health products regulatory authority annual report 2017 · 9 applications for new clinical...

Health Products Regulatory Authority

Annual Report 2017

HPRA Annual Report 2017

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Contents

2017 STATISTICS AT A GLANCE 2

CHAIRPERSON’S STATEMENT 3

AUTHORITY MEMBERS 5

MANAGEMENT COMMITTEE 6

CHIEF EXECUTIVE’S REPORT 7

HUMAN MEDICINES 11

MEDICAL DEVICES 22

BLOOD, TISSUES AND ORGANS 28

VETERINARY MEDICINES 30

SCIENTIFIC ANIMAL PROTECTION 34

CONTROLLED DRUGS AND PRECURSOR CHEMICALS 36

COSMETIC PRODUCTS 37

OTHER REGULATORY PROGRAMMES 38

OUTREACH AND ENGAGEMENT 40

ORGANISATIONAL DEVELOPMENT 43

AUTHORITY AND COMMITTEES 45

APPENDICES 47

FINANCIAL STATEMENTS (SEE SEPARATE PDF DOCUMENT)


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2017 Statistics at a Glance

20 - THE NUMBER OF PATIENTS WHO COMPLETED THE HPRA MODULE OF THE IPPOSI PATIENT

EDUCATION PROGRAMME

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4.5 - OUR ASSESSMENT RATING OUT OF 5 UNDER BEMA, THE BENCHMARKING PROGRAMME FOR

EUROPEAN MEDICINES AGENCIES

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684 - THE TOTAL NUMBER OF NEW HUMAN MEDICINES AUTHORISED

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96 APPLICATIONS ISSUED FOR CLINICAL TRIALS OF HUMAN MEDICINES

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152 NEW MARKETING AUTHORISATION APPLICATIONS ISSUED FOR VETERINARY MEDICINES

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9 APPLICATIONS FOR NEW CLINICAL INVESTIGATIONS OF MEDICAL DEVICES

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131 MANUFACTURING LICENCES IN PLACE AT YEAR END – 111 FOR HUMAN MEDICINES AND 20

FOR VETERINARY MEDICINES

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3,857 EXPORT CERTIFICATES ISSUED – 1,486 CERTIFICATES FOR MEDICINES AND 2,371 FREE SALE

CERTIFICATES FOR MEDICAL DEVICES

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29 EU PSUR SINGLE ASSESSMENT PROCEDURES FOR HUMAN MEDICINES LED BY THE HPRA

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4,402 SUSPECTED ADVERSE REACTION REPORTS FOR HUMAN MEDICINES RECEIVED

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397 REPORTS OF SUSPECTED ADVERSE REACTIONS ASSOCIATED WITH USE OF VETERINARY

MEDICINES

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2,339 MEDICAL DEVICE VIGILANCE REPORTS RECEIVED AND ASSESSED

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1,281 MARKET SURVEILLANCE CASES UNDERTAKEN IN RESPECT OF MEDICAL DEVICES

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89 MEDICINE RECALLS CONSISTING OF 82 HUMAN MEDICINES AND 7 VETERINARY MEDICINES

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118 GMP INSPECTIONS CONDUCTED AT MANUFACTURING SITES FOR HUMAN AND VETERINARY

MEDICINES, AND ACTIVE SUBSTANCES

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3 REGULATORY INFORMATION SEMINARS HOSTED – IN LEITRIM, LIMERICK AND DUBLIN – FOR OUR

COSMETIC STAKEHOLDERS

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200,000 UNITS OF ILLEGAL PRESCRIPTION MEDICINES DETAINED IN IRELAND DURING PANGEA X

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Chairperson’s Statement

It is a great pleasure to introduce the 2017 annual report, which outlines the extensive work of the

HPRA over the past 12 months.

As Chair of the HPRA, I see my role as being to work with the members of the Authority to support the

Chief Executive and the members of the executive team in our mission to continually protect and

enhance public and animal health. As outlined in my report last year, we are guided by our strategic

plan and we depend ultimately on having dedicated, qualified and experienced staff to deliver on our

ambitions. This is how we ensure that the highest standards of excellence and capabilities are

maintained and continually evolve so as to meet all our stakeholders’ needs into the future.

In order to measure our effectiveness as an organisation, we engage in external benchmarking

programmes with our counterparts across Europe. The learnings from such reflective and thorough

analysis continue to drive the HPRA’s ambition to deliver better outcomes for patients and members

of the public.

In this respect, I would like to highlight two significant developments in 2017; our involvement in the

Joint Audit Programme (JAP) for inspections and our participation in the Benchmarking of European

Medicines Agencies (BEMA).

The European Heads of Medicines Agencies (HMA) Joint Audit Programme is an external

benchmarking process. The HPRA’s quality system for good manufacturing practice (GMP) –

incorporating inspection and licensing of manufacturers of medicines, management of quality defects

and recalls, and sampling and analysis of medicines – was evaluated under this programme in May.

The audit was observed by the US FDA as part of its review of equivalency of our systems in relation to

the US/EU mutual recognition agreement (MRA) on GMP inspections. The audit was successful,

validating the strength of the HPRA’s processes and procedures for inspection and quality defect

management. As a result, I look forward to the significant achievement of Ireland’s anticipated

inclusion as a country recognised under the MRA during 2018.

This was followed in October by the HPRA’s participation in BEMA, the benchmarking programme for

European human and veterinary agencies which is now in its fourth cycle. This programme aims to

contribute to the development of a world-class pharmaceutical regulatory system across Europe,

based on a network of agencies consistently employing recognised best practices. The HPRA’s

assessment, which was carried out by representatives from three other EU regulatory agencies,

resulted in an excellent overall rating of 4.5 (out of 5). Of particular note, there was a top rating of 5

for nine specific indicators.

One of those indicators related to human resources and I am very proud of the emphasis that the

Authority places on the development of its most important asset, its staff. In 2017, we saw the second

year of activity under the organisation’s HR Strategy and the commencement of the HPRA’s

Management Development Programme focusing on developing leadership capabilities and talent

management. This investment in our people managers is central to developing the internal capabilities

across the organisation for now and into the future. Investment in technical expertise was also a key

priority in 2017.

As an organisation, the HPRA always strives to develop new approaches to foster engagement and

ensure we best serve public and animal health. For many reasons 2017 was a notable year in this

regard. For example, as outlined by our Chief Executive in her 2017 Report, the management of Brexit

and its potential implications in terms of medicines availability, has brought about the need for a

different approach to our engagement with patients and healthcare professionals for the purposes of

ensuring effective management of this situation.


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The Authority also recognises the importance of transparent and open communication with our

stakeholders, especially patients, healthcare professionals and members of the public. During 2017, a

number of new initiatives were progressed to enhance and develop our communications. I look

forward to working further with the Authority and HPRA staff in shaping and evolving the work that

has commenced and I intend to report more fully on this in next year’s annual report.

Forward Focus

Looking ahead, the members of the Authority and I are ever conscious that the HPRA faces a range of

opportunities and challenges in 2018. These include management of a changing complex regulatory

environment in Europe across many areas including medical devices, clinical trials and veterinary

medicines, supporting innovation and, of course, Brexit. All of these activities will be addressed and

prepared for alongside the critical routine work of the organisation and its ongoing development of

capabilities and support services. We are greatly assured by the expertise, preparedness and

pragmatic approach of the agency staff in addressing its many priorities.

Over the coming years, working together, we will ensure that the HPRA remains alert and agile with

the capability and capacity to anticipate and meet the demands of a rapidly changing external

environment. As always, we remain fully committed to our constant and common goal of protecting

the health and safety of all those who use health products.

Acknowledgments

On behalf of the Authority, I thank the Minister for Health, the Minister for Agriculture, Food and the

Marine, their advisors and the staff of their departments for their ongoing support of the HPRA and its

activities.

I would particularly like to thank the Chief Executive, management and all the staff and to

acknowledge the excellence of their work. The very significant progress and results achieved in 2017

are clearly reflected throughout this report.

On a personal note, as Chairperson, I would like to express my gratitude to the members of the

Authority for their expert input and support throughout 2017. Finally, my thanks also to the Chairs and

members of the HPRA advisory committees and sub-committees. The contribution of all the

independent experts who give freely of their expert opinion and time is of huge value to our

organisation.

Ann Horan

Chairperson


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Authority Members

The Authority of the HPRA is appointed by the Minister for Health in accordance with the powers

conferred by subsection 2 of section 7 of the Irish Medicines Board Act, 1995. There were nine

Authority members up to 31 December 2017.

Ms. Ann Horan

Chairperson

Mr. Pat Brangan

Mr. Wilfred J. Higgins

Mr. David Holohan

Professor Mary Horgan

Mr. Brian Jones

Professor Elizabeth Keane

Professor Caitriona O’Driscoll

Dr. Diarmuid Quinlan


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Management Committee

Dr. Lorraine Nolan

Chief Executive

Ms. Rita Purcell

Deputy

Chief Executive

Dr. J.G. Beechinor

Director of

Veterinary Sciences

Dr. Jayne Crowe

Director of Human Products

Authorisation and Registration

Dr. Caitríona Fisher

Director of Quality, Scientific

Affairs and Communications

Dr. Joan Gilvarry

Director of Human

Products Monitoring

Mr. Kevin Horan

Director of ICT and

Business Services

Mr. John Lynch

Director of

Compliance

Ms. Lynsey Perdisatt

Director of Human

Resources and Change


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Chief Executive’s Report

In preparing my third foreword to the Annual Report since I was appointed as Chief Executive in

January 2016, I have been struck by how it has been a very busy year that has seen many new

opportunities and developments emerge. It continues to be my privilege to lead a dynamic Agency

that makes a major and tangible contribution every day to safeguarding public and animal health in

Ireland and beyond.

2017 resulted in some clear step changes for the Health Products Regulatory Authority (HPRA) and

the continued progression of our organisation in line with the goals set by our 2020 Strategic Plan.

During the year, we made significant inroads in advancing our processes for direct engagement with

patients and the public, healthcare professionals and innovators. I believe that this progress brought

about in 2017, which is further expanded below, is changing the way in which we are connecting with

our key stakeholders and is delivering more meaningful two way engagement. In addition to

positioning the HPRA as being accessible and approachable in terms of our remit of protection of

public and animal health, developments in 2017 have ensured that the value-add of our regulatory

approach continues to be better understood by our stakeholders. It has also played a significant role

in informing us on how we should continue to grow and develop our organisation into the future.

Stakeholder Engagement and Communications

One of the developments from 2017, which I am particularly proud of, was the execution of our role as

an education partner in the Irish Platform for Patient Organisations, Science and Industry (IPPOSI)

Patient Education Programme. The HPRA’s contribution focused on the areas of regulatory affairs,

medicinal product safety and pharmacovigilance. This initial programme, tailored for Irish patient

communities, concluded with the graduation of 20 expert patients who will play an important role in

sharing their knowledge and experiences for the benefit of others.

The HPRA, through our colleague Almath Spooner, the Vice-Chair of the Pharmacovigilance Risk

Assessment Committee (PRAC), was centrally involved in the first ever public hearing at the European

Medicines Agency (EMA) held in September. This unique opportunity to give EU citizens a voice in the

evaluation of the safety of medicines and empower them to express their views on issues related to

the management of risks, is something to emulate at national level. In 2017, our mechanisms for

engagement with patient groups and healthcare professionals have been further enhanced to involve

greater use of multi-stakeholder discussion forums for key medicines safety issues. This is something

we believe will better serve the public as it will deliver greater alignment between health product

regulation and healthcare provision.

As an organisation, the HPRA is completely committed to ensuring that the market for health

products in Ireland is highly and appropriately regulated to enable the highest standards of public and

animal health protection. Consistent with this, we continue to apply our expertise to ongoing safety

assessment and monitoring of authorised medicines on the market whilst utilising our regulatory

powers as required. Simultaneously, we place considerable focus on minimising the entry of illegal

medicines to the marketplace. In this regard, Operation Pangea again highlighted the significant

collaboration taking place between the health product regulators, law enforcement agencies and the

private sector in combating the illegal supply of medicines and medical devices on an annual basis.

The 2017 operation, which represented the tenth year of Pangea, took place in September 2017, and

was led by the HPRA in partnership with Revenue’s Customs Service and An Garda Síochána. It

resulted in the detention of over 200,000 units of illegal prescription medicines, a threefold annual

increase. This outcome was a result of enhanced intelligence-led enforcement activities building

successfully on our strong year-round collaboration with our partner agencies. Globally, Pangea led to


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over 25 million illegal medicines and medical devices worth over US$56 million being detained across

123 countries. Significantly, from a public health perspective, this enforcement operation also

provided the HPRA and our partner organisations with a key opportunity to highlight the serious risks

involved in sourcing illegal prescription medicines and medical devices online, many of which are from

dubious sources and may be counterfeit.

Supporting Innovation

In 2017, we also continued to identify ways to support and facilitate product development for patients

in need of new treatments by further improving early engagement with key stakeholders. The

Innovation Office at the HPRA was established in late 2016 with our first innovation stakeholder event

to provide a platform for sharing knowledge and information taking place in May 2017. The

conference brought together researchers, entrepreneurs and other interested parties from various

sectors including academia, research organisations, SMEs and the life sciences industries. Enhancing

communication and strengthening the links between academia, industry and regulators is a critical

support for a sector which is highly dynamic and innovative. This area was a key focus for us during

the year as we continued to build on our programme of outreach with the sector which first

commenced in 2016.

Our focus on innovation also extended to involve greater contribution at European level, through the

Innovation Network, and internationally. Specifically, we assumed a role in supporting innovation

through our participation in the International Coalition of Medicines Regulatory Authorities (ICMRA)

which established a new strategic priority in innovation during the year. This priority includes a work

stream, focusing on outcomes of horizon scanning, which is jointly led by the HPRA and the EMA.

BREXIT

Many of the advancements we made in 2017 were brought about as part of our proactive approach to

managing the significant challenges presented by the United Kingdom’s decision in 2016 to withdraw

from the EU. Our focus since this announcement has always been, and will continue to be, public

health protection. The HPRA hosted a Brexit stakeholder event in August 2017, the first such event

hosted by a competent authority in Europe. Brexit has potentially significant implications for the

European regulatory network as a whole and particularly for Ireland given our shared marketplace

with the UK. We have confirmed our commitment to support the European network to ensure that the

resources and capacity required are available to guarantee an orderly redistribution of the work

currently undertaken by the UK and we will continue to position our agency to swiftly contribute to

addressing any additional issues that may arise from the UK’s exit. Through this preparedness, and our

support of the EMA’s relocation to Amsterdam, we will assist the smooth continuation of EMA

activities and help to deliver the network’s shared goal of protecting human and animal health in

Europe at all times. Nationally, the HPRA is fully committed to working to ensure that the availability

of medicines and other health products is not negatively impacted by Brexit and we have been

proactively focused on supporting measures to ensure sustainable levels of product marketing

authorisations in Ireland.

One of the consequences of Brexit is that the EMA has to relocate from its present location in London.

During 2017, the HPRA, working with colleagues from the Department of Health and IDA Ireland, as

well as other Government officials and diplomats in Brussels and throughout Europe, led the

development of a proposal to have the Agency relocated to Dublin. Ireland was one of nineteen

countries that submitted proposals to the European Commission. The decision was subsequently

made through the European Council in September and Amsterdam was chosen as the new location

for the Agency. The HPRA looks forward to supporting both the EMA and the European network in

ensuring a successful transition to the new location in the Netherlands which will begin during 2018.


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Although Dublin was not the chosen location, the preparation of the proposal, the strength of which

was recognised by numerous stakeholders, was a unique opportunity to showcase the many strengths

of Ireland in relation to the wider life sciences sector, our access to scientific talent and the strong

regulatory environment that has been established by the HPRA. It was a great pleasure to work with

our Government colleagues on this project, which was of significant strategic importance from the

perspective of public health and promoting Ireland’s economic interests and reputation

internationally.

Separate to Brexit, but nonetheless related, the HPRA established a new project on medicines

shortages in 2017. This followed a request by the Department of Health for the HPRA to undertake a

role in the national coordination of medicines shortages following a review it convened under its

Medication Safety Forum. Due to a range of factors, medicine shortages are increasing in prevalence

and affecting all the global regions. The HPRA-led project is focused on developing enhanced

methods and devising new solutions to ensure better coordination among key stakeholders in Ireland

for both the prevention and management of medicines shortages. The objective is to develop a

national protocol for management of shortages to ensure better patient outcomes and enhanced

communication and engagement on this key public health issue.

Building Internal Capabilities

The environment in which we operate is fast paced, dynamic and evolving. Our strategic goals drive us

to develop our internal capabilities and plan for future expertise requirements in line with the constant

development of new and innovative health products and technologies. In the past year, our focus has

been on attracting new talent with diverse and expert skills in the areas of software, analytics and new

areas of clinical interest. In addition, we have continued to invest in the development of the skills and

expertise of our staff. 2017 saw further developments under our HR strategy, which sets out a five-

year roadmap for talent development within the HPRA. Key deliverables achieved last year include the

launch of our Management Development Programme.

All the while, our regulatory environment continues to evolve. Indeed, during 2017, political

agreement was reached on the new medical devices regulatory framework for Europe. This is a

significant development in further strengthening the regulatory environment within which we operate

to provide further protection for patients and users of medical devices. It also requires the HPRA to

continue to evolve and develop our approach so that as an organisation we can continue to deliver a

robust system of regulation for medical devices which meets current and future needs. A key focus for

the year ahead will be reshaping our internal structures and processes for medical devices to allow us

to effectively deliver our remit in the context of the revised framework and, most importantly, to best

serve the needs of Irish patients.

Network Participation

Throughout the year, the agency has worked very closely with our European counterparts through

representation on a wide range of committees and working groups at the EMA and within the Heads

of Medicines Agencies’ network, as well as at a bilateral level. HPRA representatives continue to hold

the substantial roles of Chair of the EMA’s Committee for Medicinal Products for Veterinary Use

(CVMP) and Vice-Chair of the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC).

We have also continued to grow our participation and footprint within international networks through

our work in the International Coalition of Medicines Regulatory Authorities and the International

Medical Device Regulators Forum. The work of both these groups aims to enhance global

harmonisation among regulators. As an agency, we are honoured to be the host and are very much

looking forward to the World Health Organisation’s International Conference of Drug Regulatory


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Authorities (ICDRA) in Dublin in 2018 and work continued during the past year in preparation for this

major event.

A Look Forward

The HPRA regulates a wide range of health products in Ireland. Indeed, as a regulator of ten classes of

health products across nine regulatory regimes, we have one of the widest remits when compared to

other agencies internationally. We set ourselves high standards and are well placed to continue on our

planned development trajectory. To achieve our potential, we must reflect on our achievements in

2017 and plan for the known and indeed the unknown opportunities and challenges that lie ahead.

Our investment in building internal capabilities, stakeholder engagement and innovation supports,

position us well as we continue on our journey to meet the challenges of being a regulator of the

future.

Acknowledgments

I would like to thank and acknowledge the support and co-operation of the Ministers and staff of the

Department of Health and the Department of Agriculture, Food and the Marine during 2017.

On behalf of our management team and all our colleagues, I also wish to thank the members of the

Authority and advisory committees for their continued contribution and commitment to the HPRA.

Their independent expertise and advice is of huge value to our agency. My particular gratitude to the

Authority Chairperson, Ann Horan, and the Authority members for their support and dedication

throughout the year.

I must expressly thank my colleagues within the HPRA for the tangible results and achievements

outlined in this annual report. It clearly reflects the expertise, commitment and professionalism

displayed across the organisation as we both delivered on our planned work programme and

responded to the opportunities and challenges that arose.

The HPRA is the agency it is because of all those who contribute to its work: the members of the

Authority, scientific committees and advisory groups, our staff, Management Board and national

experts, and all our stakeholders who share their views and experiences to help us deliver on our

absolute commitment to protect public and animal health.

Lorraine Nolan

Chief Executive


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Human Medicines

The HPRA grants licences for medicines subject to a review of their safety, quality and effectiveness

and continuously monitor their use once they become available on the Irish market. We also approve

and monitor clinical trials, inspect and license manufacturing sites and wholesalers, and investigate

activities associated with the illegal supply, manufacture or advertising of medicines.

AUTHORISATION AND REGISTRATION

Prior to a new medicine being placed on the Irish market, it must be assessed and authorised

(licensed) by the HPRA or by the European Medicines Agency (EMA) in conjunction with the

European Commission. The assessment involves establishing that a medicine’s health benefits

outweigh its known risks. Where this is the case, it may be granted a marketing authorisation.

There are a number of routes through which a product can be authorised by the HPRA. These

include the national procedure, the mutual recognition procedure (MRP) and the decentralised

procedure (DCP). Both MRP and DCP involve the simultaneous submission of applications in a

number of EU Member States.

The centralised route is coordinated by the EMA and results in an authorisation which is granted by

the European Commission and is valid across Europe. The assessment is carried out by Member

States appointed as lead assessor (rapporteur), joint lead assessor (co-rapporteur) and peer

reviewer, with input also from all other Member States.

During the year in review, the total number of new medicines authorised in Ireland was 684. This

compares to 637 in 2016. The 2017 figures incorporate:

- 104 new national applications which incorporates 99 parallel import applications;

- 58 applications made under the MRP and 324 applications made under DCP. The HPRA acted

as reference (lead) Member State for the assessment of 12 of the DCPs.

- 2 rapporteurships and 10 co-rapporteurships under the centralised route. A number of these

applications were for biological medicines.

- An additional 186 medicines authorised through the centralised route where the HPRA was

neither rapporteur nor co-rapporteur.

In 2016, we established a new national scientific advice procedure to assist commercial and non-

commercial entities in the development of new or existing medicines or making applications for

clinical trial authorisation or marketing authorisations. This service complements advice which we

provide on earlier stage product development through the Innovation Office as well as scientific

advice provided at an EU level through the EMA’s Scientific Advice Working group. During the year:

- We continued a pilot study in 2017 based on a number of national scientific advice meetings.

Six meetings were held as a result of which we were able to review the cumulative experience

gained over the nine months of the pilot.

- Our external guidance document for stakeholders was revised and published to our website.

- Initial discussions were held with the National Centre for Pharmacoeconomics in late 2017 in

respect of horizon scanning, early scientific advice, the EMA-EUnetHTA three-year work plan

and patient education.

Timely access to medicines is critical for patients so they can benefit from new and promising

therapies and a number of procedures are available to assist in this.

- The HPRA secured its first rapporteurship for a medicine under the EMA’s PRIME scheme

which offers early support to developers so they are better positioned to generate robust data


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on the medicine and enable accelerated assessment of the marketing authorisation

application.

- A total of 96 new clinical trial applications were issued in 2017; 19 of these applications were

voluntary harmonisation procedures for clinical trials with the HPRA acting as lead Member

State for five of these co-ordinated work-sharing assessments for multinational clinical trials.

Reclassification of the legal status of medicines aims to increase the number of medicines available

to patients without prescription where it is safe to do so. This year:

- One prescription-only medicine for pain relief was authorised for non-prescription, pharmacy-

only sale while another pharmacy-only medicine, indicated for nicotine replacement therapy,

was reclassified to general sale.

In June 2013, the HPRA commenced publication of a list of interchangeable medicines to facilitate

generic substitution by pharmacists and to allow for reference pricing by the Health Service

Executive (HSE). By year end, the interchangeable medicines list included 60 active substances.

A biosimilar medicine is a biological medicine that is very similar to an original biological medicine

called the reference medicine.

- During 2017, we published an online questions and answers document which was developed

in plain English and approved by the National Adult Literacy Agency (NALA) prior to

completion in November. In addition, we commenced work on a plain English video.

- Also in November, the HPRA hosted a successful information evening for healthcare

professionals to outline how biosimilar medicines are approved for use in patients.

- During the year, we delivered a series of presentations at external events to inform healthcare

professionals and patients about the use of biosimilars. Staff members also contributed to a

number of peer-reviewed papers and conference papers that focused on this topic.

- The HPRA’s biosimilars project in conjunction with Regulatory Science Ireland was successfully

completed in 2017 with all elements of the work plan accomplished. The research scientist

who commenced work on this project in January 2016 submitted her thesis entitled ‘The

Regulatory Science of Biosimilars’ to University College Cork in December 2017.

Medicine shortages have been an ongoing concern globally and in Ireland for some years. Under

our current strategic plan, we have committed to establishing a system for co-ordinating the

management of shortages. During 2017:

- We commenced a project, following Department of Health approval, to design and implement

a system for co-ordinating the management of shortages. In Q4, we conducted an intense

phase of stakeholder engagement, meeting with patient groups, healthcare professional

groups, the HSE and various industry associations to gather their experience and perspectives

about the reasons for shortages and the appropriate management of them.

- In light of potential shortages arising from the response of companies to the exit of the UK

from the EU, we also began discussions with other regulatory authorities with a view to

developing harmonised product information and joint packaging. There were bilateral

meetings/contacts throughout the year between the HPRA and the MEB (Netherlands) and

the MPA (Sweden) to discuss labelling issues and work sharing opportunities. Discussions are

also ongoing with the UK in this regard. There is a general consensus that in so far as possible

we should continue with joint labelling and maintain the close communication between both

agencies.

We continued to monitor the numbers of unauthorised products notified to us through the exempt

medicinal product scheme. One aspect of our approach to reducing the risks to patients is to

actively seek new marketing authorisation applications for high-volume products currently being


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imported through this scheme. One application was received by year end and is being considered.

It is anticipated that this will be assessed under an accelerated procedure.

In November 2016, the Minster for Health requested the HPRA to provide scientific advice in

respect of the potential medical use of cannabis. The HPRA convened an expert working group to

assist with its review of this matter. The HPRA report – Cannabis for Medical Use: A Scientific

Review – outlines the key findings and conclusions of the working group. Following approval by

the Authority of the HPRA on 25 January 2017, the report was presented to the Minister for Health

on 31 January and published on the HPRA website. The HPRA then commenced a series of

engagements in respect of the report findings and met with a number of patient and public

representatives. The HPRA also appeared before the Oireachtas Joint Committee on Health to

discuss the report on 7 March.

The Minister for Health endorsed the HPRA report and established the Cannabis Reference Group

during 2017 to prepare clinical guidance and develop a national Cannabis Access Programme to

enable access to cannabis for medical use. In conjunction with stakeholders, including the HPRA,

the Department of Health is developing the Cannabis Access Programme and the Statutory

Instruments to underpin the programme.

Authorisation and registration: Key figures

2015 2016 2017

Classification queries 80 49 34

Scientific advice

Lead in EMA scientific advice:

National scientific advice (commenced in 2016)

39

--

51

13

47

6

Clinical trial applications 108 108 96

Voluntary Harmonisation Procedures (multinational

clinical trials)

Lead

Participating member state

8

15

8

22

5

14

New medicines applications for marketing authorisations

National

Mutual recognition and decentralised RMS

Mutual recognition and decentralised CMS

Centralised Rapp/Co-Rapp/Peer reviewer

137

17

422

12

71

12

365

20

104

10

370

12

Traditional herbal medicinal products under the simplified

registration scheme 7 9 4

Homeopathic medicines under the simplified rules scheme 0 1 2

Variations to marketing authorisations (Type IA, IB, II) 14,461 13,837 11,600

Articles 45 and 46 - Variations to Update Product

Information 1 1 2

Renewals of marketing authorisations 322 351 248

Transfer of marketing authorisation holder 245 209 208

Parallel product authorisations 125 57 99

Manufacturers 95 103 111

Manufacturers of investigational medicinal products 52 55 52

Wholesalers 287 318 348

Registrations for active pharmaceuticals ingredients

Manufacturers

22

21

28


14

Importers

Distributors

37

37

41

49

59

81

Brokers 1 3 9

Export certificates 1,646 1,274 1,375

Exempt medicines programme for notification of

unauthorised medicine import

1,639,312

packs

1,827,047

packs

1,961,54

1 packs

SAFETY AND QUALITY

Under the SCOPE project (Strengthening Collaboration for Operating Pharmacovigilance in Europe)

created to support pharmacovigilance in the following EU legislative requirements that came into

effect in June 2012:

- There was collaboration with stakeholders concerning the distribution of joint DHPCs, and

targeted communications to raise awareness of the availability of educational materials on the

HPRA website.

- We engaged with IPPOSI, as part of its pilot Patient Education Programme specifically tailored

for Irish patient communities, to provide medicines safety input for patient training materials.

- Additional modalities were explored for communication pharmacovigilance issues, including

social media platforms, focused safety alerts to stakeholders and video sharing websites, while

quality standards, ‘best practice’ and training materials were implemented.

In anticipation of the changed reporting rules for the EU’s Eudravigilance database of adverse

reactions:

- The HPRA’s own adverse reaction database was updated to ensure compliance with the new

reporting standard. This was fully operational in October, ahead of the move to centralised

reporting to the Eudravigilance in November, including an updated reporting process and

training of all staff.

- Updates were given to stakeholders to facilitate appropriate and timely testing of the new

standard and reporting arrangements, including through the Medicinal Products Newsletter

and website updates and alerts.

Adverse reactions reports assist the HPRA, in co-operation with pharmacovigilance professionals in

Europe and further afield, to look for new types of reactions or changing trends in reporting.

Reports submitted to the HPRA in many instances arise from concerns occurring during

observation of an unexpected and / or unwanted event, in the context of use of a medicine. They

also include known adverse reactions, such as those described in the product information. This

year:

- 4,402 adverse reactions reports were received associated with the use of human medicines.

This represents a 35% increase in overall reporting rates compared with 2016. While there was

already a legal obligation for marketing authorisation holders (MAHs) to report all serious

adverse reaction reports of which they become aware to the HPRA, since 22 November 2017

this requirement was extended to include non-serious reports. This change to reporting

requirements largely accounts for the increase in the volume of reports received.


15

- In the context of the changed reporting requirements, 76% of all adverse reaction reports

received by the HPRA in 2017 were reported by MAHs, with a further 1.5% reported in the

context of ongoing clinical trials. It is important to note that these reports will have initially

been notified to companies by healthcare professionals, patients or consumers. The remainder

of the reports received (22.5%) were submitted directly to the HPRA by healthcare

professionals and members of the public with almost half of these submitted through the

HPRA’s online reporting system.

- Medicines subject to additional monitoring accounted for 26% of the reports submitted.

- The medicines most frequently included in reports to the HPRA accounted for 78% of the

adverse reaction reports received in 2017 (see table). It is important to note that the place of a

medicine on this list cannot be taken as an indicator of safety or risk. The number of reports

received cannot be used as a basis for determining the incidence of a reaction as neither the

total number of reactions occurring, nor the number of patients using a medicine, is known.

Suspect Medicine(s) / Class of Medicines Number of

Reports*

Antineoplastics, including immunomodulating medicines,

monoclonal antibodies and endocrine medicines

1854

Psycholeptic medicines 453

Anti-infective medicines, including antibacterials, antimycotics,

antivirals and immunoglobulins

413

Vaccines 294

Medicines for the treatment of bone disease 193

Cardiovascular medicines, including antihypertensives and lipid

lowering agents

166

Medicines used in Diabetes 155

Medicines used to treat Parkinson’s Disease 149

Antithrombotic medicines 136

Respiratory medicines 125

2835 2884 2810

3264

4402

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

2013 2014 2015 2016 2017

Adverse Reaction Reports


16

- Of the new adverse reaction reports received by the HPRA in 2017, 262 patients were reported

to have died while on treatment. The table below outlines the medicines or class of medicines

associated with the highest number of reports. In many of these cases, the patients had

significant underlying illness and were treated with multiple medicines and/or surgery which

may also have contributed to the outcome. In addition, many of these cases were influenced

by disease progression or other complications unrelated to the medicine. The majority were

associated with medicines subject to close monitoring, those used in the management of

severe underlying medical conditions, in patient support programmes and special patient

monitoring programmes.

Suspect Medicine(s) / Class of Medicines Number of

Reports*

Antineoplastics, including immunomodulating medicines,

monoclonal antibodies and endocrine medicines

114

Psycholeptic medicines 31

Antithrombotic medicines 19

Analgesic medicines 16

Anti-infective medicines, including antibacterials, antimycotics,

antivirals and immunoglobulins

15

Parenteral nutrition preparations 10

Cardiovascular medicines, including antihypertensives and lipid

lowering agents

8

Respiratory medicines 6

Medicines for the treatment of bone disease 5

Radiopharmaceuticals for treatment of cancers 4

*Please note that in some cases treatment may have involved more than one medicine from the groups

listed.

The HPRA also plays a key role in monitoring the safety of medicines on the Irish market via our

vigilance assessment and risk management activities. This incorporates our contribution to the

work of the Pharmacovigilance Risk Assessment Committee (PRAC) at the EMA. During 2017, the

HPRA:

- Continued our involvement in the work-sharing initiative for signal detection within the EU

acting as lead Member State for the monitoring of 54 nationally-authorised active substances.

Serving as PRAC rapporteur, we were also responsible for the further management of any

signals detected in relation to 44 centrally authorised medicines (containing 28 active

substances / combination of active substances).

- Participated in the EU periodic safety update report (PSUR) single assessment procedure,

contributing to the evaluation of 941 PSURs and leading the single EU assessment for 29 of

these procedures.

- Participated as a concerned Member State in 13 newly initiated safety referrals seven of which

reached a conclusion during the year.

- Contributed to the review of 154 risk management plans (newly approved or updated)

submitted via national, mutual recognition, decentralised and centralised procedures. We also

provided assessment input to 348 post authorisation safety study procedures (protocols,

reports and other post authorisation safety-related measures).


17

The inspections and audits programme focuses on ensuring industry compliance with relevant

standards and legislation. This year, there were:

- 106 good manufacturing practice (GMP) inspections were conducted at sites that produce

human medicines or active substances.

- 183 good distribution practice (GDP) inspections at wholesalers and distributors;

- 13 good clinical practice inspections;

- 4 pharmacovigilance inspections.

The HPRA’s risk based sampling and analysis programme is part of our monitoring of the quality

and safety of medicines on the Irish market or which are manufactured in Ireland for export. It

involves the analytical testing of products and / or examination of their packaging and labelling. A

total of 288 samples were taken under the programme in 2017. This included:

- The examination of the packaging and labelling of 136 medicines and other products

available on the Irish market. A total of 35 non-compliances were identified including Braille-

related issues, non-compliant packaging and labelling, and the absence of updated safety

information. Appropriate follow-up actions were taken in each case.

- Additionally, 128 medicines and other product samples for human use were sent for analytical

testing during the past year. Although the majority of the samples tested were compliant with

their specifications, a number of out-of-specification results were also obtained. The most

frequent of these related to product appearance not being in accordance with the

specification. Again, appropriate follow-up actions were taken in each case.

The quality defect and recall programme investigates, on a risk basis, reports of suspected quality

defects in medicines and in their related active substances. It also co-ordinates recalls from the

Irish market. Quality defects pertaining to 650 medicines for human use were reported or

identified in 2017. The risk classifications that were assigned, along with the corresponding figures

for the previous two years, are outlined in the accompanying table.

As in previous years, companies (65%), including manufacturers, distributors and/or authorisation

holders, and other competent authorities (27%) were the primary sources of received reports.

In certain cases, it may be deemed necessary to withdraw, or recall, medicines from the Irish

market in order to protect public health. During the year, 82 medicine recalls occurred

representing a 59% decrease when compared to 2016 (when an unusually high number of recalls

occurred due to distribution issues). Overall, the most common causes of recalls during 2017

were:

Year 2015 2016 2017

Critical quality defects 213 119 124

Major quality defects 218 331 196

Minor quality defects 301 382 327

Number of reports not justified 5 3 3

Total Number Quality Defects 737 835 650


18

Cause of Recall Human Medicines

Erroneous distribution activities 11

Stability issues 11

Non-compliance with variations 7

Lack of sterility assurance 9

Other non-compliance with GMP 6

Non-compliance with SPC/printed artwork 5

Non-compliance with specifications 5

Adverse reactions or changes in benefit/risk ratio 4

Primary/secondary packaging component issues 4

One of the mechanisms used by the HPRA to aid continuity of supply to the market place in the

event of a medicine shortage includes the granting of a temporary authorisation for a batch of a

medicine known as a ‘batch specific request’. In 2017, there were 115 requests received.

The HPRA monitors the general retail sale of consumer healthcare products in outlets such as

grocery shops, health food shops and, where necessary, pharmacies. This year, 73 cases, some of

which involved multiple products, were investigated. Of these,

- 34 related to the sale of medicines that did not carry a valid registration number or

authorisation number for the Irish market.

- 22 related to proactive monitoring of compliance of retailers in the sale of certain medicines

with additional restrictions; and

- 17 related to the sale of products that had been incorrectly classified as non-medicines by

those placing them on the market.

A total of 57 medicines that did not carry a valid registration or authorisation for the Irish market

were removed from sale with 11 of these medicines subject to prescription control.

Three regulatory compliance inspections were conducted at the premises of marketing

authorisation holders to determine the level of compliance with the legal requirements for the

marketing and advertising of medicines.

The advertising compliance programme monitors and reviews advertising and promotion

activities by the industry for compliance with the legislation. This year 334 advertisements were

reviewed, and non-compliances, including both major and minor issues, were identified in 160 of

these. In all cases, the HPRA oversaw the necessary corrective and/or preventative actions for

those issues, where relevant. Eight advertisements were recalled. (The HPRA has published a

standalone report available from our website which provides an overview of the main elements of

the advertising compliance programme for 2017).

Under our enforcement programme:

- The HPRA detained 948,915 dosage units (including tablets, capsules and vials) of falsified and

other illegal medicines last year compared to 673,906 units in 2016 – an increase of more than

40%. The products detained, through both ongoing surveillance and targeted intelligence

based operations, included anabolic steroids (47%), sedatives (23%) and erectile dysfunction

medicines (13%). There was a significant rise in the number of anabolic steroids detained


19

rising from 109,006 in 2016 to 449,411 dosage units in 2017. Separately, a total of 3,866

enforcement cases were initiated, compared to 4,054 in the previous year.

- In one operation of particular significance, over 60,000 vials labelled as containing anabolic

steroids were detained as part of a joint operation carried out with An Garda Síochána and

Revenue’s Customs Service at a number of locations in County Donegal. Other medicines,

including human growth hormone and products indicated for erectile dysfunction, were also

found. The total value of illegal medicines detained was estimated to be in excess of €2

million.

- We initiated six prosecution cases and issued six voluntary formal cautions. Prosecutions are

taken where the HPRA considers that there is a significant risk to public health. The 2017

prosecutions related to the unauthorised supply of prescription medicines, including anabolic

steroids and erectile dysfunction products. The HPRA also supports prosecutions brought by

the Director of Public Prosecutions in relation to the illegal supply of medicines.

- The HPRA, in partnership with Revenue’s Customs Service and An Garda Síochána, detained

over 200,000 units of illegal prescription medicines in Ireland, valued at over €850,000, as part

of the Interpol-coordinated Operation Pangea X. The products detained included significant

volumes of anabolic steroids, sedatives and erectile dysfunction medicines. Nationally, the

week-long operation also resulted in two arrests, the investigation of 38 websites and eight

social media pages being taken offline. Operation Pangea X was an international week of

action across 123 countries to tackle the online sale of counterfeit and illicit medicines and

highlight the dangers of buying medicines online.

LEGISLATION AND REGULATION

The new Clinical Trial Legislation, Regulation EU No 536/2014, was originally intended to be

implemented throughout the EU by October 2018 but this timeline has been deferred due to

delays in building the online portal for applications at the European Medicines Agency.

Notwithstanding these European delays, some national activities have been progressed during

2017:

- We engaged with the Department of Health and HIQA regarding the implementation of the

Regulation and the development of national legislation.

- We developed a pilot scheme (for commencement in January 2018) for simultaneous

submission of applications to both the HPRA and ethics committee which will enable

preparation for implementation of the Regulation. Guidance and templates for sponsors were

published in December.

- We actively participated in the European voluntary harmonisation project which is similar to

the approval process for clinical trials under the planned new legislation (see page 12).

From 9 February 2019, under the Falsified Medicines Directive, medicines must carry special safety

features in the form of an anti-tamper device and a barcode containing ‘unique identifiers’

(including a serial number) to enable the authenticity of the pack to be checked prior to

dispensing. This year:

- Updates in respect of the national implementation and introduction of these measures,

including the establishment of the National Medicines Verification Organisation’s repository,

were given to industry stakeholders at the HPRA’s Good Manufacturing Practice (GMP) and

Good Distribution Practice (GDP) information days which took place on 7 and 8 February.

- The EU working group, led by the HPRA, on supervision of the national repositories of unique

identifiers developed a work plan for the project with agreed outputs and timelines for

completion.


20

We participated in audit teams as part of the Joint Audit Programme (JAP) of GMP inspectorates of

competent authorities. This also included the allied Joint Reassessment Programme (JRP) of the

Pharmaceutical Inspection Co-operation Scheme (PIC/S).

STAKEHOLDERS AND PARTNERS

As previously outlined (see page 13), the HPRA appeared before the Committee on Health in early

March along with officials from the Department of Health to discuss the report – Cannabis for

Medical Use: A Scientific Review. The HPRA Chief Executive, who was accompanied by the Clinical

Assessment Manager, outlined the report findings and recommendations which were finalised

following input from an expert working group comprising relevant clinical experts and patient

representatives. The HPRA representatives provided responses to a number of queries from the

Committee members.

In May, the HPRA’s Director of Human Products Monitoring joined experts from the Department

of Health, the Royal College of Physicians in Ireland and the HSE in addressing members of the

Committee on Health on the issue of vaccine uptake levels. Among the topics discussed were the

huge positive public health impact of vaccination, how the safety of vaccines are monitored on an

ongoing basis, and issues related to the fall in the numbers receiving the HPV vaccine in the

recent past.

As in recent years, the HPRA delivered a programme of presentations and talks at external

stakeholder events such as meetings, seminars, conferences and training courses. Such

presentations provide stakeholders such as healthcare professionals and regulatory professionals

with access to relevant, up-to-date information. In addition, a programme of presentations was

delivered to undergraduate and postgraduate students studying courses related to the role of the

HPRA. A full list of all presentations delivered during 2017 relevant to human medicines is

provided in Appendix 2.

Publications and Information

- The Drug Safety Newsletter provides important safety information to healthcare professionals

with hyperlinks to product information and other relevant documents on the HPRA and EMA

websites. Seven issues of the newsletter were published and distributed to registered

healthcare professionals, all of which are accessible from the HPRA website. A full index of

topics covered during the past year is included in Appendix 3.

- Risk communications:

o During 2017, 106 new or updated educational materials were approved by the HPRA

in addition to 21 direct healthcare professional communications.

o The PRAC monthly agendas, minutes, meeting highlights, notifications of safety

reviews and signals were also made available via our website.

- There were a number of articles provided for inclusion in the monthly MIMs (Ireland)

publication in addition to articles for the Irish Medicines Formulary. The full list of topics

covered in these articles is included in Appendix 3.

- The Medicinal Products Newsletter provides regulatory news and updates for those working

in the pharmaceutical industry. Three editions were published on our website in 2017 and are

available to download from the ‘Publications’ section.

- Three new guidance documents relevant to human medicines were published in 2017 and are

available to download from our website:

o Guide to Scientific and Regulatory Advice for GXP activities

o Guide to Clinical Trials Regulation (EU) No. 536/2014 Pilot Project

o HPRA Brexit Guidance


21

HPRA information seminars and training events provide regulatory guidance and updates to a

range of stakeholders. Our programme of events in 2017 included:

- The biennial good manufacturing practice (GMP) and wholesale distribution information days

which were held on consecutive days in February and attracted a combined attendance of

almost 650 industry representatives.

- A GMP inspector training course, organised by the HPRA on behalf of PIC/S, which took place

in Dublin from 23 to 27 October and was attended by 34 GMP inspectors from 17 countries.

- An information day in November for stakeholders on the HPRA’s regulatory compliance

inspection and advertising programmes. This was attended by over 140 industry

representatives.


22

Medical Devices

As the national competent authority for medical devices, the HPRA carries out a range registration,

surveillance, monitoring and compliance activities. Our aim is to make sure that these products

perform as intended and do not compromise the health and safety of the patient or the person using

them.


The HPRA is focused on ensuring effective and consistent designation and oversight of notified

bodies at national and European level. In 2017, we:

- Continued our schedule of oversight of the notified body in Ireland based on ongoing

assessment, surveillance and observed audits.

- Provided expert assessors to participate in four EU joint assessments of notified bodies based

in other European countries. Since the scheme’s introduction in 2013, the HPRA has provided

the highest number of expert assessors to this programme compared to other EU countries.

- Continued to provide leadership and support development of EU coordination of notified

body designation and oversight by acting as the deputy chair for the EU Notified Body

Operations Group (NBOG) and participated in the core EU Joint Assessment Coordination

Group (JACG).

- Identified and prioritised development of systems and resources at national and EU level to

allow, from November 2017 onwards, timely and effective designation of notified bodies

required under the new EU Device Regulations (EUDR).

Supporting innovation and research of new technologies is a key strategic priority for the HPRA

devices team. In 2017, this involved:

- The review of applications to conduct clinical investigations of medical devices in Ireland. The

number of clinical investigations taking place continues to increase with nine new applications

and six amendments to ongoing investigations received in 2017. The HPRA continue to focus

on this area to ensure regulatory requirements and processes are clear to potential applicants.

- Organising a medical device innovation workshop in Galway hosted by the NUIG Clinical

Research Facility in conjunction with the CURAM and BioInnovate facilities. The workshop was

attended by over 50 innovators, researchers and clinicians.

- Encouraging engagement during product development and innovation of medical

technologies. During 2017, we met with 16 groups of innovators (13 preliminary and three

pre-submission meetings).

- Supporting the work of the HPRA Innovation Office by responding to around 40% of all

queries received.

- Presenting and participating in innovation sessions at a variety of conferences and workshops

including the EuroPCR conference in Paris.

In 2017, the HPRA received 31 registrations of new organisations manufacturing self-declared

medical devices in Ireland. A total of 362 new self-declared medical devices were also registered.

Additionally, during the year we developed a comprehensive listing of economic operators within

the medical device sector in Ireland (manufacturers, authorised representatives, distributors) to

allow for better planning and coordination of our market surveillance activities.


23

SAFETY AND QUALITY

We continue to develop and reinforce our market surveillance activities, with particular emphasis

on proactive rather than reactive actions. Of note in 2017:

- We launched a new lifecycle market surveillance strategy and planning mechanism to ensure

continued safety and performance of devices throughout their lifetime.

- We led or participated in various elements of both technical work packages of the EU Joint

Action on Market Surveillance (JAMS) of medical devices initiative which is funded by the

European Health Programme. In 2017, we hosted two workshops in Dublin and attended a

further two in London involving delegates from 17 European countries with a view to:

o developing a process for coordination of EU level market surveillance issues;

o identifying a single secure communication platform for information sharing

o developing a process, best practices and training for joint manufacturer inspections;

o developing a process for prioritisation of devices requiring common specifications.

- We continued our participation in the European COEN Joint Action 2014 on reusable and re-

sterilisable medical devices. In 2017, seven Irish based manufacturers were audited as part of

the programme. One of these audits was conducted jointly with assessors from other Member

States. In addition, the HPRA participated in one joint audit of a manufacturer in another

Member State during 2017.

- A total of 43 COEN notices were sent to the European network relating to medical device

compliance concerns arising from HPRA activities while five information notices were

published in relation to medical device issues.

- There were 1,281 market surveillance cases* undertaken in 2017. The decrease in cases, when

compared to 2016, is the result of a 26% decrease in the number of EU notifications received

by the HPRA relating to notified body certificates. This decrease is likely as a result of the

success of the joint assessment scheme. During 2017, the HPRA increased the number of

other market surveillance cases by 24%, including technical file and clinical evaluation review

cases. Such cases are more resource intensive and complex than certificate notification cases.

*Please note that from the start of 2014, the HPRA changed the way we define market surveillance cases

and so the figures in the graph have been adjusted* by applying the pre-2014 definition to allow for

comparison with 2012 and 2013 figures.

We continued to focus our vigilance activities during 2017 on the areas of user reporting and

dissemination of HPRA medical device safety communications. This included:

865 902

1283

1448

1281

0

200

400

600

800

1000

1200

1400

1600

2013 2014 2015 2016 2017

Market Surveillance Cases


24

- The receipt and assessment of 2,339 medical device vigilance reports representing a 6%

increase on 2016. Of the reports notified to the HPRA, 12% came from users of medical

devices. Manufacturers accounted for 62% of reports received in 2017 while 30% came from

other competent authorities.

- There were 278 product removals conducted in Ireland during 2017. The HPRA also issued 89

national competent authority reports.

- Surgical devices, orthopaedic devices and infusion devices accounted for 42% of the total

vigilance reports. Reports continue to be received relating to diagnostic imaging and

radiotherapy devices. In addition, we continue to receive reports relating to revision

procedures associated with the ASR Articular Surface Replacement and ASR XL Acetabular

system manufactured by DePuy. During the year, we also continued development work on

signal detection of medical device issues.

As part of its market surveillance activities, the HPRA undertakes proactive and ‘for-cause’ audits of

manufacturers, notified bodies and authorised representatives with the objective of monitoring

compliance of devices emanating from Irish based organisations. During 2017, 22 audits were

performed at both medical device manufacturers and authorised representative facilities, of which:

- three were for cause audits, one of which was in the US;

- eight were reactive audits based on vigilance / market compliance issues;

- sixteen were audits based on proactive market surveillance projects – including the EU joint

action (COEN JA2014);

- two audits were conducted joint with other EU and international regulatory authorities.

433

348

287

239

177

7962 62 61 57 53

0

50

100

150

200

250

300

350

400

450

500

Vigilance Reports Received - Top 10 Product Types


25


Following publication of two new European Regulations on medical devices in May 2017, the HPRA

continued its work to help ensure an effective and timely implementation of these EU Device

Regulations (EUDR) at national and European level. This included:

- Developing internal resources, procedures and systems to ensure notified body requirements

could be applied at national level from November 2017.

- Assisting the Department of Health in the development of relevant national legislation (S.I. No.

547 of 2017) to nominate the HPRA as the National Competent Authority (NCA) for medical

devices and the authority responsible for notified bodies in Ireland.

- Preparing detailed information relating to the new requirements with respect to the need for

national legislation, the timelines and impact on existing national legislation.

- Contributing to the European development of the secondary legislation required to enable

notified body provisions to become applicable on time from 26 November 2017.

- Accepting nominations to represent Ireland at the newly established EU Medical Device

Coordination Group (MDCG) and as part of the Regulatory Committee which decides on

secondary legislation for the new EUDR. The first meeting of the MDCG took place in late

November 2017.

- Participating in the EU steering group for development of the new European database (MDR

EUDAMED) envisaged by the new Regulations. The HPRA also participated in a number of the

associated technical working groups on certificate & registration, UDI and clinical aspects with a

view to developing the system requirements and functional specifications.

- Participating in the development of Competent Authorities for Medical Devices (CAMD)’s

Frequently Asked Questions on transition to the new legislation, which are now published on

the CAMD website.

We continued to engage with the Department of Health throughout 2017 on policy and legislative

issues. Of note, a national fee-based funding model for medical devices was implemented in

January to recover the costs associated with our medical device activities. Fees were confirmed for

all economic operators (manufacturers, authorised representatives and distributors) in Ireland.

Further information and feedback received from the sector obtained during 2017 will be used to

inform future revisions to the model which will be subject to further public consultation during

2018.

The HPRA continues to play a significant role in the development of EU regulatory systems and

mechanisms to promote coordination, cooperation and consistency. During 2017, we:

- Participated as a member of the Executive Group of the Competent Authorities for Medical

Devices (CAMD) network. This group has successfully worked in partnership with the EU

Commission over the last number of years to develop the regulatory system in Europe.

- Proposed the establishment of an Implementation Task Force (ITF) at the CAMD to identify

priorities for EU work on implementation, provide a forum for discussion and consensus on

interpretation of the new Regulations, and establish a mechanism for engagement with

stakeholders on implementation. During 2017, the HPRA acted as interim chair for this

taskforce, which published the European Implementation Roadmap in October.

- Contributed to the design and delivery of training on notified body joint assessments to

authority expert assessors at the EU Commission’s premises in Grange, Co. Meath.

- Continued to lead the work of the clinical investigation and evaluation working group, acting as

the co-chair of the group along with the EU Commission.

The HPRA continued to participate actively in initiatives to promote regulatory convergence and

harmonisation of medical devices globally through the International Medical Device Regulators

Forum (IMDRF). This involved:


26

- Participation in the IMDRF Management Committee as part of the European delegation (along

with the EU Commission, France and Germany).

- Continuing to act as the IMDRF secretariat for the National Competent Authority Report (NCAR)

Exchange programme. We also participated in a number of different IMDRF working groups

including the group on regulated product submissions (RPS) and medical device registries.

- On behalf of the EU, we officially observed two Medical Device Single Audit Programme

(MDSAP) assessments of manufacturing sites witnessing the performance of the auditing

organisations. The HPRA also observed the assessment by a MDSAP consortium of an applicant

auditing organisation.

- Contributing to briefings for the EU Commission for the purposes of the MDSAP Regulatory

Authority Committee discussions and also encouraged discussions at EU level to further

Europe’s future engagement in the programme.

We have an ongoing focus on horizon scanning and on developing our capabilities to effectively

regulate new and emerging technologies. During 2017:

- Team members researched and attended training courses in a number of medical technology

areas including software, cybersecurity and additive manufacturing.

- The Advisory Committee for Medical Devices (ACMD) established a new subgroup on medical

device software and cybersecurity with a view to identifying challenges and regulatory /

guidance needs.

- The HPRA also assumed a leadership role in Europe, chairing the software classification

subgroup of the EU classification borderline working group.

- We presented at a number of conferences and engaged with companies adopting additive

manufacturing techniques (such as 3D printing) and were part of a cross-organisational horizon

scanning project to examine and report on the regulatory aspects of additive manufacturing.


We continued to invest in stakeholder engagement and communication with medical devices

stakeholders throughout 2017. This involved the promotion of direct reporting of incidents and

medical devices issues by device users and members of the public. We also continued our

engagement with health services and healthcare professionals to encourage reporting and raise

awareness of the roles and activities of the HPRA. Work was undertaken with the HSE to identify

mechanisms and identify appropriate individual contacts to facilitate dissemination of safety

information on medical devices to the relevant health services/users (designated person and

vigilance liaison officers). We also continued to promote the adoption and communication of the

HPRA step-by-step guide to user reporting which is targeted at healthcare providers.

The HPRA undertook a number of communication initiatives to raise awareness of the impact and

requirements being introduced as a result of the new EUDR. During 2017, we:

- Established a dedicated section on HPRA website regarding EUDR. This incorporated

stakeholder guidance and application forms for notified bodies to reflect the new requirements

for designation to EUDR by the November timeframe.

- Published a dedicated newsletter and other information resources to raise awareness of specific

aspects of the Regulations and its practical application. These included specific information

leaflets targeting medical device innovators and also the cosmetic industry (given the inclusion

under the new device Regulations of certain aesthetic products).

- Contributed to the development and actively participated in two European stakeholder days on

the new EUDR hosted by the EU Commission and CAMD.

- Provided briefings, advice and workshops on the new Regulations to a range of different

stakeholders including notified bodies and distributors.


27

Throughout the year, we engaged in ongoing strategic, operational and communication initiatives

on a bilateral and multilateral basis with European and international authorities, and the EU

Commission. We also further developed our bilateral partnerships with a number of those

authorities. In addition, we participated in operational and strategic discussions on developing

cooperation between the CAMD and the Heads of Medicines Agencies (HMA) networks.

The HPRA continues to deliver a programme of presentations and talks at a range of external

stakeholders. A full list of all presentations related to the regulation of medical devices that were

delivered during 2017 is provided in Appendix 2.

Medical Devices: Key Figures

2015 2016 2017

Lead Competent Authority role on specific vigilance issues 74 98 89

NCARs and vigilance related communications 79 116 96

Vigilance cases received/opened 2,140 2,242 2,339

Field safety notices uploaded 474 476 519

Medical device safety notices 33 46 44

Medical device targeted healthcare professional communications 11 33 23

NCARs managed as IMDRF NCAR secretariat - 18 8

COEN reports (market surveillance and vigilance) to EU network 12 45 44

Medical device information notices 3 0 5

Market surveillance cases (unadjusted) 324 335 411

Notifications relating to notified body certificates 959 959 844

Classification requests 54 35 51

Compassionate use applications 3 5 5

Medical device free sale certificates 2,601 2,122 2,371

Medical device queries received 459 477 496


28

Blood, Tissues and Organs

The HPRA is responsible for monitoring the safety and quality of blood and blood components and of

tissues and cells. Along with the HSE, we are joint Competent Authority for organs intended for

transplantation.


The authorisation of blood establishments, tissue establishments and organ procurement

organisations / transplantation centres permits those facilities to carry out specified activities. The

total number of authorisations in place at year end for the past five years is presented by category in

the accompanying table.

Number of Authorisations 2013 2014 2015 2016 2017

Blood establishments 4 4 3 3 3

Tissue establishments 23 24 24 25 25

Organ procurement/transplantation 0 0 4 4 4

SAFETY AND QUALITY

Following collaboration with the National Haemovigilance Office (NHO), we submitted an annual

report of serious adverse reactions and events to the EU Commission during 2017. The report

reflected information received by the NHO in 2016 and included information on 61 serious adverse

reactions and 152 serious adverse events which met the mandatory legislative reporting

requirements.

We also submitted an annual report on serious adverse reactions and events associated with

tissues and cells to the EU Commission during 2017. The report reflected information received in

2016 and consisted of some 112 reports, 103 of which met the legislative reporting requirements,

including seven serious adverse reactions and 96 serious adverse events.

The Joint Action on Vigilance and Inspection for the Safety of Transfusion, Assisted Reproduction

and Transplantation (VISTART) promotes and facilitates the harmonisation of inspection,

authorisation and vigilance systems in the EU for blood, tissues and cells used in transfusion,

transplantation and assisted reproductive technology. As part of the HPRA’s contribution to

VISTART activities, we are leading Work Package 9 which involves a voluntary programme of inter-

member state inspection systems auditing. Consequently, we carried out a pilot audit in Q3 using

tools developed under this work package. In Q4, we also conducted an audit of the relevant

Latvian authority as part of the pilot phase of the VISTART project.

We continued to liaise with the HSE lead and colleagues from Organ Donation and Transplant

Ireland (ODTI) in relation to our respective roles under EU and national legislation on the Quality

and Safety of Human Organs intended for Transplantation. During 2017, this included:

- The exchange of relevant information on serious adverse reactions and events. During 2017,

the HPRA received 13 reports of serious adverse reactions and events associated with organ

donation / transplantation;

- The ongoing review of procedures and guidance incorporating the finalisation of updates to

the report form which were completed by year end;

- The submission of proposals to the OTDI in respect of updating the framework for quality and

safety.


29

As part of our regulatory role, the HPRA inspects relevant establishments, organisations and

centres to monitor compliance with applicable EU guidelines on the quality and safety of blood,

blood products, tissues and cells, and human organs intended for transplantation. Our inspection

programme in 2017 consisted of:

- 19 tissue establishment inspections of which four were non-routine;

- 7 routine inspections of blood establishments; and

- 1 routine inspection of an organ establishment.


As part of our ongoing contribution to the review of relevant legislation, we provided feedback to

the Department of Health on draft SIs for transposing EU Directives on coding and import for

human tissues and cells.

In relation to assisted human reproduction, we engaged with the Department of Health during

2017 to discuss the development of assisted human reproduction legislation including the

proposed regulatory agency. We also engaged in respect of the commencement of parts 2 and 4

of the Children and Family Relationships Act.


30

Veterinary Medicines

Our role is to grant licences for veterinary medicines subject to a review of their safety, quality and

effectiveness. We continuously monitor their use in animals once they become available on the market

in addition to authorising clinical field trials and inspecting / licensing manufacturing sites.


There are a number of routes through which a veterinary medicine can be authorised by the HPRA.

These include the national procedure, the mutual recognition procedure (MRP) and the

decentralised procedure (DCP). The following applications were issued by the HPRA during 2017:

- 10 new national applications;

- 75 new applications made under the DCP;

- 28 new applications made under the MRP.

We acted as reference (lead) Member State for the assessment of one of the MRPs and 30 of the

DCPs. We also issued five applications as RMS under the repeat use procedure.

The centralised route administered by the EMA is another mechanism whereby veterinary

medicines can be authorised in Ireland. In 2017, the HPRA issued 16 cases as rapporteur or co-

rapporteur for veterinary medicines. An additional 18 new medicine applications were issued

through the centralised route where we were neither the rapporteur nor co-rapporteur.

By end of year, there was a record total of some 1,700 veterinary medicines authorised for the Irish

market.

During 2017, the HPRA acted as co-ordinator for three requests under the EMA scientific advice

procedure.

Medicine shortages continue to be an issue for many veterinary practitioners tasked with treating

many different species and conditions. Problems of non-availability can arise from a number of

issues and different solutions are needed depending on the issues involved. During 2017:

- We conducted planned twice yearly reviews of AR18 and AR16 lists. The HPRA strategy is to

review incoming requests and seek Irish authorisation where practicable.

- Carried out gap analysis and prioritised applications linked to shortages.

- Meetings were held with the Department of Agriculture, Food and the Marine to discuss

shortages related issues. There was agreement to develop an inter-departmental process in

respect of potential shortages arising from Brexit.

- Communicated and met with applicants regarding transfer of reference member state (RMS)

to Ireland. We also revised the relevant procedure and established a register of products for

transfer.

- We worked closely with EU competent authorities to enable the use of common packs and

carried out a survey to explore dual labelling interest in other Member States.

Authorisation and registration: Key figures

2015 2016 2017

Classification enquiries 21 16 11

Clinical trials 0 1 2


31

New centralised as (co-)rapporteur 11 11 16

New MR/DCP as RMS 15 14 30

New MR/DCP as CMS 93 78 44

New homeopathic applications 6 0 3

New national applications 5 8 8

Renewals, national and MR 88 100 108

Variations, national and MR 1431 1341 1366

Manufacturers of veterinary medicines 25 24 20

Export certificates 99 155 111

SAFETY AND QUALITY

The operation of a national pharmacovigilance system for veterinary medicines is dependent on

the submission of reports by veterinarians, pharmacists, licensed merchants and others involved in

dispensing or using the medicines concerned. These reports may be submitted either directly to

the HPRA or to the companies marketing the medicines. The companies, in turn, must relay the

data to the HPRA.

Over the course of 2017, we received 397 national reports of suspected adverse events to

veterinary medicines with the vast majority of reports, as in previous years, received from

pharmaceutical companies.

We evaluated 630 periodic safety update reports (PSURs) which incorporated the assessment of

individual medicines on the market in Ireland as well as a work-sharing initiative where we led, or

contributed to, the assessment of a class of veterinary medicines for the European Union.

Containment of the development of antimicrobial resistance (AMR) is essential for public and

animal health. Our work in this area includes the collection of annual information on the sale of

veterinary antibiotics from each marketing authorisation holder. This information, which is included

in the European Surveillance of Veterinary Antimicrobial Consumption (ESVAC), is important as it

allows us to benchmark our usage rate against those of our European neighbours and to follow

271300

435

337

397

0

50

100

150

200

250

300

350

400

450

500

2013 2014 2015 2016 2017

Adverse Event Reports


32

any developing trends. The data show that due to a variety of factors there are significant

fluctuations in sales annually and, consequently, that a clear trend is not identifiable.

Veterinary antibiotic use 2012 2013 2014 2015 2016

Tonnes sold 97.4 99.1 89.4 96.9 103.4

Additionally in 2017, we continued our participation in the National Interdepartmental

Antimicrobial Resistance Consultative Committee which in October published ‘Ireland's National

Action Plan on Antimicrobial Resistance 2017-2020’.

The analytical testing of products is a key component of the HPRA’s risk based sampling and

analysis programme. A total of 31 samples of veterinary medicines were taken under the

programme in 2017 and all were subject to laboratory testing. Although the majority of the

samples tested were compliant with their specifications, a number of issues, such as the crumbling

of tablets, were noted. Appropriate follow-up actions were taken as necessary.

We investigate, on a risk basis, reports of suspected quality defects in medicines and active

substances, and co-ordinate subsequent recalls from the Irish market where necessary. There were

48 quality defects pertaining to medicines for veterinary use reported or identified in 2017. The risk

classifications that were assigned, along with the corresponding figures for the previous two years,

are outlined in the accompanying table.

Companies, including manufacturers, distributors and/or authorisation holders, accounted for 64%

of the reports received with the balance received from other competent authorities.

In certain cases, in order to protect animal and / or public health, it is deemed necessary to

withdraw, or recall, a veterinary medicine from the Irish market. In 2017, seven recalls of medicines

occurred which was one less than the previous year. Of these, three were recalled due to stability

issues.

Our inspections and audits programme focuses on ensuring industry compliance with relevant

standards and legislation. In 2017, there were:

- 12 good manufacturing practice (GMP) inspections conducted at sites that produce / test

veterinary medicines;

- 2 pharmacovigilance inspections.

Year 2015 2016 2017

Critical quality defects 1 7 5

Major quality defects 8 12 13

Minor quality defects 25 22 30

Number of reports not

justified 1 0

0

Total Number Quality Defects 35 41 48


33


We continued to engage with the Department of Agriculture, Food and the Marine in respect of

the proposed new EU veterinary medicines legislation. Meetings were held to review the proposals

and we presented feedback on each Commission revision. We also met before year end to

consider the European Council discussions on the new legislation. The Department participates at

Council meetings.


As part of our ongoing stakeholder engagement, in 2017:

- We conducted a survey during Q2 in respect of outgoing MR/DCP applications to determine

stakeholder perceptions of the HPRA‘s service levels and performance, and to assess their

communication needs and expectations. Analysis of the results were completed by year end

and the findings will be used to inform future service provision and communications.

- We held meetings with a number of stakeholders during the year as part of our review and

audit of the current level of national regulatory and scientific advice provision at each stage of

product development.

- We are committed to participating in activities that promote pharmacovigilance reporting, in

particular with respect to food-producing species. During the year, we developed a training

proposal and submitted a draft training module to a third level institute for review and

consideration.

- As part of our commitment to enhance our stakeholder communication on safety issues, we

developed and published a number of safety notices on our website in relation to vaccine

shortages and topics including euthanasia, zinc oxide and monitoring of medicines.

Throughout 2017, we continued our involvement across the EU regulatory network which includes

active participation at the EMA and the HMA. Of particular note, Dr David Murphy continued to

serve as Chair of the EMA’s Committee for Medicinal Products for Veterinary Use (CVMP) following

his election in 2016.

As in recent years, we delivered a programme of presentations to veterinarian students and

veterinary nursing students on the role of the HPRA and the promotion of veterinary

pharmacovigilance. We also presented at a number of industry stakeholder events. A full list of all

presentations delivered during 2017 is provided in Appendix 2.

We continued during 2017 to publish relevant content in our Medicinal Products Newsletter. This

newsletter provides updates for those working in the veterinary medicines sector on Irish and

European legislation, new / revised HPRA regulatory publications and stakeholder events such as

information days. Three editions were published on our website in 2017 and are available to

download from the ‘Publications’ section.

We also contributed a number of articles to the Veterinary Ireland Journal and the It’s Your Field

publication. Details are included in Appendix 3.


34

Scientific Animal Protection

The HPRA is the competent authority in Ireland responsible for the implementation of EU legislation

(Directive 2010/63/EU) for the protection of animals used for scientific purposes.


The HPRA carries out evaluations of applications for the authorisation of research establishments

and projects in addition to evaluating applications from individuals to allow them to conduct

procedures or euthanasia of animals. As shown in the accompanying table, there was an increase

in both the total number of individuals and projects authorised in 2017. Please note that the

higher level of individual authorisations during 2013 and 2014 was due to the legal requirement

for existing establishment personnel to apply for individual authorisations, which are valid for five

years, before the end of 2014.

In October, we published the fourth annual statistical report on the use of animals for scientific

purposes in Ireland. The HPRA is required to collect and make publicly available, on an annual

basis, statistical information on the use of animals in procedures, including information on the

actual severity of the procedures.

Authorisation and registration – Key 2017 figures:

Individual authorisations 319

Project authorisation 125

Individual amendments 74

Project amendments 186

Establishment renewals 22

481 518

323

271

319

72

128114 102

125

0

100

200

300

400

500

600

2013 2014 2015 2016 2017

Authorisations

Individuals

Projects


35

SAFETY AND QUALITY

During 2017, there were 33 inspections completed, of which 18% were unannounced, to monitor

animal welfare standards and compliance with legislation. This total incorporated 25 establishment

authorisation inspections and eight compliance inspections.

One of the HPRA’s responsibilities in respect of scientific animal protection is to grant permission

to rehome animals if certain criteria are met that protect and provide for the animal’s overall well-

being. Early in 2017, we approved a pilot rehoming scheme for a group of dogs from Charles River

Laboratories as a result of the closure of a facility in County Mayo. Following the positive outcome

of the pilot, when a number of dogs were effectively rehomed through animal welfare

organisations, the rehoming scheme was subsequently extended. It was concluded after the

successful rehoming of 342 dogs and 249 cats confirming it as one of the largest projects of its

kind ever undertaken.


In May, in co-operation with the Health Research Board and Science Foundation Ireland, we hosted

a 3Rs conference in Croke Park, Dublin. The conference presented over 200 delegates with

information and recommendations on how to apply the 3Rs to research with the aim of improving

animal welfare and achieving better science.

We published and disseminated three regulatory updates to provide stakeholders with the latest

news and guidance from the HPRA, with information on education and training, and with information

and best practices in respect of the 3Rs and compliance with the legislation.

In December, we delivered a Laboratory Animal Science and Training (LAST) lecture in relation to

the legislative and regulatory aspects of scientific animal protection.


36

Controlled Drugs and Precursor Chemicals


Import, export and holding of controlled drugs (for legitimate purposes) are subject to licensing.

The Department of Health is the licensing authority while the HPRA handles the administrative

aspects of the application and licensing process. Licensing activity consists primarily of export and

import licences, and letters of no objection. Data for the past five years are outlined in the

accompanying graph.

The HPRA is the licensing authority for precursor chemicals. These are subject to different licensing

requirements, dependant on specific categories. The following table shows the licensing activity

since 2013.

Precursor Chemicals Licensing Activity 2013 2014 2015 2016 2017

Total 27 46 32 16 23


Following commencement of the Misuse of Drugs (Amendment) Act 2016 on 4 May 2017,

changes were made to the requirements for controlled drug import and export licences. All

necessary adjustments to HPRA procedures and forms were subsequently implemented.


Prior to the commencement of the new legislation, we communicated with relevant stakeholders

to remind them that a number of substances that were not previously controlled would now fall

under the scope of the Misuse of Drugs framework. We published the relevant details in the

HPRA’s Medicinal Products Newsletter in January and this was followed by the dissemination of an

e-mail update in April. Companies were advised to review products handled to ascertain any

impact of the proposed changes and to update procedures and authorisations where necessary.

2055 21302363 2343

2689

0

500

1000

1500

2000

2500

3000

2013 2014 2015 2016 2017

Controlled Drugs Licensing Activity


37

Cosmetic Products The role of the HPRA is to regulate the manufacture, sale and supply of cosmetic products in Ireland.

We identify and address cosmetic product quality and safety issues, in conjunction with the HSE, so

that a cosmetic product will not compromise the health and safety of the consumer or the person

applying the product.


During 2017, we issued 174 cosmetics free sale certificates which may be required by companies

exporting products to third countries.

SAFETY AND QUALITY

As part of our proactive market surveillance activities, we conducted three inspections of cosmetic

distributors to assess compliance with the Cosmetics Regulation. Distributors were informed of any

non-compliances identified and requested to implement corrective actions.

Our reactive market surveillance includes investigation of quality-related complaints (compliance

cases), reports of adverse events relating to the use of cosmetics (vigilance cases) and serious risk

alerts received from other countries (RAPEX). In total, there was 312 reactive surveillance cases

initiated during 2017.


We developed a cosmetic products information pack which was

published in March 2017 to guide stakeholders through placing a

cosmetic for sale on the market and to provide an easy-to-use

checklist to help ensure all regulatory requirements were met

before placing a cosmetic on the market. This initiative was

undertaken as a result of direct feedback from stakeholders in

2016.

We hosted three regulatory information seminars in Leitrim,

Limerick and Dublin during October to provide cosmetic

stakeholders with useful, up-to-date information on their

responsibilities under the Cosmetics Regulation. Given that many

attendees were small businesses, we invited a member of the

Local Enterprise Office to speak at each event also. These evening

events were well attended and the feedback from stakeholders

was that the information, which included printed copies of the

information pack, was relevant and well presented.

In addition, we launched a media information campaign in December to raise awareness among

consumers of the dangers presented by counterfeit cosmetics in the run up to the Christmas

period. The information was published by both print and online media and we participated in a

number of national and regional radio interviews. Consumers were informed on how to spot a

counterfeit cosmetic and of the risks these products can pose.


38

Other Regulatory Programmes

INSPECTIONS, AUDITS AND MARKET COMPLIANCE

The Joint Audit Programme (JAP) is a key element of the quality system adopted by good

manufacturing practice (GMP) inspectorates in Europe and aims to ensure consistency of GMP

standards and a harmonised approach throughout Europe.

- A positive JAP evaluation of the HPRA was carried out from the 15 to 19 May by GMP

inspectors from Austria, France and Iceland, and an auditor from the Commission’s

Directorate General (DG) for Health and Food Safety. Our GMP inspections, manufacturers’

licensing, quality defects and recall programme, and sampling and analysis systems were

examined in addition to the legislation for both human and veterinary medicines and our

overarching quality management system. As part of the assessment, the conduct of a full GMP

inspection by the HPRA was observed by one member of the audit team.

- Also in 2017, the HPRA led two JAP evaluations of the GMP compliance programme of other

member states. One was at the State Institute for Drug Control (SIDC), the competent

authority for human medicines in the Slovak Republic, while the other was at the Agency for

Medicinal Products and Medical Devices of the Republic of Slovenia (JAZMP).

The successful completion and positive outcome of the HPRA’s JAP evaluation validates the

strength of our processes and procedures for inspection and quality defect management. Of

particular note, our audit was observed by the US FDA as part of its review of the equivalency of

HPRA systems in relation to the US/EU mutual recognition agreement (MRA) on GMP inspections.

A detailed data package was also prepared and presented to the FDA for its consideration as part

of competency assessment. The FDA subsequently confirmed that the HPRA has the capability,

capacity and procedures to carry out GMP inspections at an equivalent level. As a result, it is

anticipated that Ireland will be included on the list of recognised member states under the MRA

during 2018 and from that point forward the FDA can rely on HPRA inspections to replace its own

inspections.

Other EU contributions included leading on:

- the development of a new risk assessment tool for the selection of medicinal products and

active substances for surveillance testing;

- a new risk-based tool to support inspection and surveillance relating to heparin

manufacturers and their related products; and

- the development of a communication tool-kit for the Official Medicines Control Laboratory

(OMCL) Network.

We completed a pilot project, which commenced in 2016, on advertising compliance with regard

to advertising advisory boards. A report on the outcome of this project will be finalised in early

2018.

INNOVATION SUPPORT

Supporting innovation is one of the HPRA’s five strategic goals. This is in recognition of the pace of

development of new health products, technologies and platforms and the resulting potential to

provide huge benefits for patients. However, the changes being brought about by innovation can

also present challenges for the regulatory model as it is currently constructed. Our actions under

this theme during 2017 included the following:


39

- This was the first full year of activity for the HPRA’s Innovation Office which provides

regulatory support and advice to individuals, academics, small and medium enterprises,

pharmaceutical and medical device companies, and other groups who are developing

innovative health products or technologies. A total of 38 of queries were received, mainly

from SMEs and academia, with the majority relating to medical devices, medicines and

borderline products.

- A new formal in-house horizon scanning process was developed during 2017 to enable the

HPRA to identify, at an early stage, developments and events that may require discussions at

an EU level and potential changes to the regulatory framework. There may also be a resulting

need to develop knowledge or expertise within the HPRA or to identify and recruit external

experts. The first report produced by the horizon scanning group focused on additive

manufacturing / 3D printing. A cross-organisational group is now moving ahead with the

implementation of the report recommendations. Linked to this initiative, the EU Innovation

Network adopted a HPRA proposal concerning a roadmap for the establishment of common

approach to horizon-scanning.

- The HPRA played a leading role in setting up an innovation project among members of the

International Coalition of Medicines Regulatory Authorities (ICMRA). Following an initial

survey, we prepared a project proposal that identified three work streams that will be the

focus of future activities. One of the work streams, focusing on outcomes of horizon scanning,

is jointly led by the HPRA and the EMA.

- The HPRA provides a classification service to stakeholders for products which are on the

borderline between medicines and medical devices and other categories such as cosmetics

and food supplements. This will generally determine the legislation under which a product be

regulated. During 2017, an integrated medicines and medical devices classification system for

handling requests from stakeholders was developed to optimise the consistency of HPRA

decision-making process. This will be implemented from Q1 2018.


40

Outreach and Engagement

The HPRA is committed to a strategic focus on outreach and engagement with key partners and

stakeholders so as to enhance and maximise the effectiveness of the regulatory system.

In our outreach activities to support innovation developments in Ireland:

- The HPRA organised an innovation day in May in the O’Reilly Institute in UCD. Over 260

attendees registered for the event from various backgrounds including academia, research

networks, SMEs, other agencies with an interest in innovation and the pharmaceutical and

medical device industries. Feedback subsequent to the event was very positive with

stakeholders welcoming the HPRA’s desire to reach out and engage with innovators. Extensive

tweeting of @TheHPRA Twitter account during the day helped promote the HPRA to new

audiences.

- We participated in a number of external events to promote our supports to innovation

including the Medtech Innovation Showcase at the ‘Med in Ireland’ event organised by

Enterprise Ireland. This was attended by over 250 international companies, 70 indigenous

medtech companies and a number of other organisations focused on encouraging innovation

in Ireland. We also exhibited and presented at the ‘Taking Care of Business’ event organised

by the Department of Business, Enterprise and Innovation in November. In the same month,

the HPRA’s innovation office exhibited at the SME Information day held at the EMA.

- As part of outreach activities, we met with a variety of research bodies including the RCSI, the

Regenerative Medicine Institute (REMEDI) and the Centre for Cell Manufacturing Ireland

(CCMI). We also met with Science Foundation Ireland (SFI) and the National Institute for

Bioprocessing, Research and Training (NIBRT) to discuss HPRA supports for innovation and

areas of common interest

- The HPRA is an active participant of the Pharmaceutical Education and Research with

Regulatory Links (PEARRL) programme. As part of this initiative, four early stage researchers

were given the opportunity to work within the medicines assessment area for three months so

that they could get an understanding of the regulatory process. As part our participation in

this programme, we were involved in organisation of a regulatory science symposium in Cork

in June 2017 entitled ‘Regulatory Support of Innovation in the Pharmaceutical Industry’.

- Staff also presented on horizon-scanning and innovation supports to the National Centre for

Pharmacoeconomics and industry association meetings.

- Additionally, we commenced a review of the HPRA’s contribution to external education

programmes which incorporates consideration of the most appropriate formats for future

activities. We met with APPEL (Affiliation for Pharmacy Practice Experiential Learning) to

discuss involvement in education of pharmacists.

Stakeholder communications and engagement:

- The HPRA was pleased to participate as one of a number of education partners working with

the Irish Platform for Patient Organisations, Science & Industry (IPPOSI) to deliver a Patient

Education Programme in the area of health innovation. The programme, which was specifically

tailored for Irish patient communities, was piloted from September 2017 to March 2018 based

on a ‘blended learning’ approach consisting of e-learning and face-to-face sessions. The

HPRA module, which ran for five weeks during November and December, was focused on

regulatory affairs, medicines safety and pharmacovigilance. The programme students

completed three modules in total with the additional modules focused on clinical trials and

health technology assessments.

- The HPRA's first ever national information campaign was launched in September 2016. The

campaign, which incorporates radio, digital and print advertising, was repeated in 2017 during

March / April and again in October. The focus of the HPRA adverts is to highlight the

importance of the safe use of medicines as well as medication adherence in general. Our key


41

message to members of the public is to take care when taking medication and specifically to

be aware of and read the information and directions for use that come with every medicine.

- Throughout the year, we continued our media communications programme to proactively

communicate important safety messages and to build awareness of the role of the HPRA. We

issued 25 press releases and website statements concerning safety and regulatory issues to

ensure consumers, healthcare professionals and other stakeholders received timely and

accurate information and advice. In a number of instances, these communications resulted in

national and regional media interviews with a HPRA spokesperson. In addition, we responded

to more than 500 initial and follow-up queries from national, local and specialist media during

the year.

- The HPRA website – www.hpra.ie – is a key communications channel and we continuously

monitor and analyse key visitor and usage statistics. Among the key findings from 2017 were:

o Almost 314,000 unique visitors accessed our website during the past twelve months

representing a more than 10% increase compared to 2016.

o There were in excess of 770,623 visits in total throughout the year.

o Of those who accessed the site, close to 20% were new or first time users.

- The @TheHPRA Twitter account was launched in late 2016 as a tool to support our

communications activities and direct additional traffic to the HPRA website. We continued to

develop our Twitter activity during 2017 and by year end we had secured more than 800

followers. Among the highlights was our participation in an EU-wide social media campaign to

promote the reporting of suspected side effects from medicines. This campaign was

supported by a range of patient organisations and other national health agencies.

HPRA information seminars and training events provide regulatory guidance and updates to a

range of stakeholders. The HPRA also partners with other regulatory organisations to co-host

relevant sessions. During 2017, we hosted the following events:

- VISTART Workshops, 1 – 2 February and 30 – 31 March

- GMP Information Day, 7 February

- GDP Information Day, 8 February

- JAMS Workshops, 10 – 11 April and 30 November

- 3Rs Information Day, 17 May

- Innovation Day, 25 May

- Brexit Stakeholder Meeting, 31 August

- Cosmetic Information Days: 11 October in Carrick-on-Shannon, 12 October in Dublin and 19

October in Limerick

- Biosimilar Information Seminar, 18 October

- PICs Training, 23 – 27 October (Nibrt)

- Working Group of Quality Managers and Working Group of Communications Professionals, 27

– 29 November

- EMA QWP Assessor Training, 4 – 5 December

At European and international

- We continued providing technical assistance to the Zambia Medicines Regulatory Authority

with our consortium partners, and issued a ‘Health Systems Strengthening Programme for

Zambia’ report in June.

- In early 2017, the World Health Organisation (WHO) announced Ireland as the location for the

next International Conference of Drug Regulatory Authorities (ICDRA) which takes place in

September 2018. This WHO global event provides regulatory authorities with a unique forum

to meet and discuss ways to strengthen global collaboration in the area of medicines’

regulation. Throughout the year, the HPRA progressed planning and preparation for the five-

day conference which is expected to attract more than 300 delegates from up to 100

countries worldwide. This included a meeting in Dublin with WHO representatives where a


42

range of items were reviewed and agreed in addition to a site visit to the meeting venue. The

development of a dedicated conference website – icdra2018.ie – was also completed and

commenced taking registrations in early 2018.

- The UK withdrawal from the EU has potentially significant implications for the European health

products sector and regulatory network as a whole and particularly for Ireland with its shared

market place. Protecting the availability of medicines for Irish patients and the integrity of our

market are key strategic aims of the HPRA’s Brexit-related activities while also optimising our

role within the European regulatory network and maintaining our strong working relationships

with UK colleagues. There were a number of Brexit-related initiatives either completed or

progressed in 2017 including:

o A strategic review by the senior management of the implications of Brexit and the

resulting HPRA response. A detailed, dedicated plan was agreed focusing on five key

areas: communication, existing work, new work, stakeholder influence and resourcing.

As part of the initial rollout of the plan, an internal working group was established

with representatives from across each of the products areas regulated by the HPRA.

o In August, we held a successful stakeholder event which was attended by almost 300

delegates from the biopharma, medtech and life sciences sector. The meeting was

one of the first opportunities for stakeholders from across the sector to meet and

engage in respect of the challenges being presented by Brexit. The HPRA intends to

host further such meeting during the second half of 2018 once greater clarity on the

conditions and terms of the UK exit is available.

o The HPRA working group developed a detailed guidance document for industry

stakeholders to complement similar information published at a European level. The

guide was published in a newly established dedicated Brexit section on the HPRA

website in December.

o We participated in a number of speaking engagements to outline the potential

impact on the Irish market and the planned HPRA Brexit strategy.

o At a European level, we continue to be very active participants in initiatives and

preparations linked to Brexit. This includes our high-level contribution to EMA

activities and our membership of the HMA Brexit Task Force.

Key outreach and engagement figures 2017

Public consultations we held

- Regulatory fees

- Consultation on medical devices distributor guidance

2

Public consultations we responded to:

- Included CORU, Department of Health, European Commission;

Heads of Medicines Agency, HSE, Medical Council and PSI

12

Events managed by HPRA events teams 16

Freedom of information requests 20

Requests received in accordance with the Data Protection Acts 2

Parliamentary questions 93

Queries from government departments or members of the Oireachtas 76

Protected disclosures received by external persons under section 7(2)

of the protected Disclosures Act, of which investigation is:

- Concluded

- Ongoing

7

1

Protected disclosures from HPRA staff members 0

Complaints 0

Customer service queries 3096


43

Organisation Development

The HPRA is committed to having the necessary corporate functions, systems and supports in place to

deliver on our public health mission. We must ensure that our organisational capabilities continue to

expand and evolve in line with regulatory and scientific developments and that we adapt to other

changes in our operating environment.

The BEMA (Benchmarking of European Medicines Agencies) assessment of the HPRA’s

management systems and systems for regulating human and veterinary medicines took place on

10 to 13 October, by an assessment team from three other EU countries. The assessment against a

range of indicators was thorough and challenging, with very positive results for the HPRA,

including ‘best practices’ acknowledged in a number of areas. A small number of improvement

actions will be addressed in 2018.

During 2017, the HPRA’s quality management system continued to be extended with the

deployment of policies and procedures in preparation for the upcoming General Data Protection

Regulation, new policies on risk management, energy and the internal audit strategy, and new

procedures to better support innovation office queries and media queries. Guidance documents

for stakeholders were published on the website including a guide to the notified body designation

process, and a guide to scientific and regulatory advice for GXP activities.

We continued our preparations for compliance with the General Data Protection Regulation

(GDPR) which comes into force on 25 May 2018. This included the establishment of a data

processing register.

Management and development of our staff is

critical to the success of the HPRA’s regulatory

functions. Using a framework of six core

themes, our HR and Change Strategy 2016 –

2020 identifies and delivers key supports

required by the organisation to achieve its

goals over the coming years.

During the year:

- We established a programme to further develop

managerial capability in the HPRA and delivered

three of the six modules of the management

development programme to all managers in the

organisation.

- A strategic approach to succession planning was

developed and a key role review and forecasting analysis completed. Development plans were

agreed and are underway. In addition, we began work on developing a scientific role skills

matrix and approach agreed for the key role review.

- A new graduate recruitment programme was launched, with an 18-month programme for two

rotations to be offered to candidates in relevant scientific disciplines. By year-end, interviews

were completed and candidates identified to commence their placements in September 2018.

- We continued to deliver existing programme of activities, such as health and wellness

programmes, organisational awareness fora and lunchtime learning. The receipt of a gold

Active@work award from the Irish Heart Foundation was recognition of our efforts in this

regard.

- Our LinkedIn presence was established with online recruitment testing in progress.


44

In consideration of the changing regulatory environment for medical devices, we reviewed the

internal structures for the delivery of expanded functions with the management committee and

held a number of workshops for staff. The subsequent report presented to the Authority identified

the need for changes to the structure to allow us to effectively plan and implement the new EU

Regulations. These involve bringing together in one department all medical devices staff except for

the auditors who remain with the inspectorate section. Plans were underway by the end of the year

to begin this process and recruit a head for the new department.

IT developments

- EOLAS is the HPRA’s new workflow technology solution, which will provide the organisation

with a single workflow and data management system to support its regulatory activities. It will

also incorporate new EU standards for regulatory data management. In 2017, the system was

deployed to our Veterinary Sciences department in addition to the receipts and validations,

and quality management sections. End users were supported through the provision of both

general and role specific training and this was supplemented with training documents and

online videos. Following go-live, end users worked closely with the project team to identify

and manage any issues or adjustments required. This user insight supported ongoing

preparations for deployment in 2018 to human medicines procedures.

- There were 417,211 regulatory submissions made through the Common Electronic Submission

Portal (CESP), which is managed by the HPRA on behalf of the wider EU regulatory

community. By year-end, there were 5,000 organisations availing of CESP with over 12,000

individual users.

- The HPRA participated, as part of a European consortium, in the European Commission’s

Horizon 2020 research programme on the openMedicine project that provided

recommendations on the identification of medicines in a cross border setting, this project

concluded in 2017.

Finance

- The 2017 financial statements presented in this report were prepared and submitted for audit

to the Comptroller and Auditor General. All financial transactions during the period under

review are reflected and reported upon in these statements as is our commitment to the

highest standards of corporate governance.

- The annual review of regulatory fees for 2018 was completed following public consultation

and resulted in the introduction of a modest general fee increase. Fees had not been

increased by the HPRA since 2010 with reduced fees introduced both in 2011 and 2012.

- Invoicing was introduced to support the introduction of a fee based funding model for the

HPRA’s regulatory functions in respect of medical devices. The finance team engaged with

relevant stakeholders as necessary in respect of the fees issued and payments received while

monitoring the collectability rate on an ongoing basis.

The HPRA, as a public sector body, is required to report annually on its energy usage and actions

taken to reduce consumption in accordance with the European Union (Energy Efficiency)

Regulations 2014 (S.I. No. 426 of 2014). As an organisation, we use electricity for lighting, air

conditioning or heating as required and the provision of hot water; natural gas is used for central

heating. In 2017, the HPRA consumed 804.5 MWh* of energy consisting of:

- 600.5 MWh of electricity

- 203.9 MWh of fossil fuels

- 0 MWh of renewable fuels.

*these figures may differ from those officially published by the SEAI – official figures were not available at

time of printing.


45

Authority and Committees

The Authority of the HPRA met six times in 2017 and considered a number of strategic matters

including corporate policy, planning and financial matters. The latter included monthly

management accounts, annual budgets and the financial statements for 2016. The Authority also

reviewed update reports from the Statutory Advisory Committees and the Audit and Risk

Committee. In addition, it reviewed the licences for all medicinal healthcare products as approved

by the Management Committee.

The number of meetings attended by each Authority member during 2017 was as follows:

Authority Member

Number of meetings

held during the

period the member

was on the Authority

Number of meetings

attended during the

period the member

was on the Authority

Ms. Ann Horan (Chairperson) 6 5

Mr. Pat Brangan 6 6

Mr. Wilf Higgins 6 6

Mr. David Holohan 6 6

Prof. Mary Horgan 6 2

Mr. Brian Jones 6 6

Prof. Elizabeth Keane 6 6*

Prof. Caitriona O’Driscoll 6 6

Dr. Diarmuid Quinlan 6 5*

*One via T/C

- The Audit and Risk Committee, a subcommittee to the Authority, met four times in 2017.

Further details are provided in the HPRA’s Financial Statements.

- The Advisory Committee for Human Medicines met on one occasion in 2017. The Clinical

Trials Sub-Committee is a sub-committee to the Advisory Committee for Human Medicines

and it met twelve times in the past year.

- The Advisory Committee for Veterinary Medicines met twice as did the Advisory Committee

for Medical Devices.

- The National Committee for the Protection of Animals Used for Scientific Purposes, a statutory

committee to provide guidance to the regulator and those working in this area, met twice in

2017.

Decisions of the Authority:

The terms of reference of the Authority, which are published on the HPRA website, include an

overview of how the Authority operates, an overview of all decisions taken by the Authority and those

devolved to the Management Committee.


46

The following decisions are reserved functions of the Authority:

- The Authority takes decisions relating to very significant and serious public and/or animal

health matters except in circumstances where a meeting of the Authority cannot be

convened, in which case the Management Committee takes the decision and informs the

Chairperson at the earliest opportunity and the Authority as soon as is practical.

- The Authority refuses applications, or suspends, revokes or terminates authorisations as

set out in legislation except in circumstances where:

(a) the urgency is such that a meeting of the Authority cannot be convened, or

(b) the application or authorisation is subject to a binding European decision, or

(c) the application or authorisation is for a clinical trial or clinical investigation; in which

case the Management Committee takes the decision and informs the Authority.

- Through its Audit Committee, the Authority approves the internal financial controls and

the financial audit function and satisfies itself that the financial controls and systems of

risk management are robust and defensible. The Authority appoints the internal financial

auditor.

- The Authority approves the investment policy, major investments, capital projects and the

terms of major contracts.

- Significant acquisitions and the disposal or retirement of assets above a threshold set by

the Authority are subject to Authority approval.

- The Authority approves treasury policy and risk management policies.

- The Authority approves corporate plans as required.

- The Authority approves the annual budget, monitors expenditure and supervises the

preparation and submission of the annual statutory accounts.

- The Authority makes an annual report on the activities of the HPRA, including a financial

statement, to the Minister for Health. This report is then published.

- The Authority selects and appoints the Chief Executive, with the consent of the Minister

for Health. The terms of office and the remuneration of the Chief Executive are

determined by the Minister for Health, after consultation with the Authority and with the

consent of the Minister for Finance. The Authority, through its Performance Review

Committee, conducts a process of annual performance appraisal of the Chief Executive.

Succession planning for the role of Chief Executive is also undertaken by the Authority.


47

Appendix 1 – Committee Members

MANAGEMENT COMMITTEE

Dr Lorraine Nolan

Chief Executive

Ms. Rita Purcell

Deputy Chief Executive

Dr Gabriel Beechinor

Director of Veterinary Sciences

Dr Jayne Crowe

Director of Human Products Authorisation and Registration

Dr Caitríona Fisher

Director of Quality, Scientific Affairs and Communications

Dr Joan Gilvarry

Director of Human Products Monitoring

Mr Kevin Horan

Director of Information Technology and Business Services

Mr John Lynch

Director of Compliance

M. Lynsey Perdisatt

Director Human Resources and Change

AUTHORITY (BOARD)

Ms Ann Horan – Chairperson

Dr Patrick Brangan

Mr Wilfrid Higgins

Prof Mary Horgan

Mr David Holohan

Mr Brian Jones

Prof Elizabeth Keane

Prof Caitriona O’Driscoll

Dr Diarmuid Quinlan

AUDIT COMMITTEE

Dr Patrick Brangan – Chair

Mr David Holohan

Prof Elizabeth Keane


48

ADVISORY COMMITTEE FOR HUMAN MEDICINES

Prof Mary Horgan – Chair

Dr Kevin Connolly

Prof Desmond Corrigan

Ms Maria Egan

Prof Tom Fahey

Prof David Kerins

Ms Fionnuala King

Prof Patrick Murray

Dr Fionnuala Ní Ainle

Dr Brian O’Connell

Mr Ronan Quirke

Dr Patrick Sullivan

ADVISORY COMMITTEE FOR VETERINARY MEDICINES

Dr Patrick Brangan – Chair

Dr Ruadhrí Breathnach

Ms Eugenie Canavan

Dr Martin Danaher

Dr Helena Kelly

Dr Nola Leonard

Dr Bryan Markey

Dr Ciaran Mellett

Dr Warren Schofield

Dr Robert Shiel

Dr Christina Tlustos

ADVISORY COMMITTEE FOR MEDICAL DEVICES

Mr Wilfrid Higgins – Chair

Prof David Barton

Dr Vivion Crowley

Mr Ger Flynn

Dr Fergal McCaffrey

Ms Margaret O’Donnell

Prof Martin O’Donnell

Prof Richard Reilly

Prof Mary Sharp

Mr Sean-Paul Teeling

Prof Sean Tierney


49

CLINICAL TRIALS SUB-COMMITTEE OF THE ADVISORY COMMITTEE FOR HUMAN MEDICINES

Dr Patrick Sullivan – Chair

Dr Liam Bannan

Dr Geraldine Boylan

Dr Paul Browne

Dr Peter Crean

Prof Lee Helman (CT Expert)

Dr Filip Janku (CT Expert)

Dr Catherine Kelly

Dr Patrick Morris

Dr Thomas Peirce

Dr Bryan Whelan

Dr Jennifer Westrup

EXPERTS SUB-COMMITTEE OF THE ADVISORY COMMITTEE FOR HUMAN MEDICINES

Prof Mary Horgan – Chair

Dr Linda Coate

Dr Kevin Connolly

Mr James Colville

Dr Noreen Dowd

Dr Stephen Eustace

Prof Stephen Flint

Dr Tim Fulcher

Dr Joseph Galvin

Dr Patrick Gavin

Dr Paul Gallagher

Dr Kevin Kelleher

Dr Catherine Kelly

Dr Mary Keogan

Prof David Kerins

Dr Mark Ledwidge

Dr Frank Murray

Dr Yvonne O’Meara

Dr Cormac Owens

Dr Jogin Thakore

Dr Gerry Wilson

ADVISORY SUB-COMMITTEE FOR HERBAL MEDICINES

Prof Des Corrigan – Chair

Dr James Barlow

Dr Kevin Connolly

Mrs Ingrid Hook

Ms Claudine Hughes

Ms Anna-Maria Keaveney

Dr Celine Leonard

Dr Donal O’Mathuna

Dr Camillus Power

Dr Helen Sheridan

Dr Emma Wallace


50

Appendix 2 – Presentations 2017

THIRD LEVEL PRESENTATIONS

Institution Course Presentation Title

Athlone IT Veterinary Nursing Regulation of Veterinary Medicines

DIT Medical Device

Decontamination (CPD)

Medical Devices Legislation / Medical Devices

Vigilance

EU Network

Training Centre

Training Champions

Workshop

Scientific and Regulatory Training for Veterinary

Medicines

IT Sligo

Medical Biotechnology

and Pharmaceutical

Science

GMP, Quality Defects, Biological Medicines and

Pharmacovigilance (Case Study based

Workshop)

Letterkenny IT Veterinary Nursing Regulation of Veterinary Medicines

NUIG / IT Sligo Medical Technology

Regulatory Affairs Medical Devices Legislation

RCSI Nurse/Midwife

Prescribing The Role of the HPRA and Pharmacovigilance

RCSI Pharmacy Quality Defect in Medicines

RCSI Pharmacy Regulation of Similar Biological Medicines

RCSI Pharmacy Regulation of Biotechnology Therapeutics

RCSI Pharmacy Regulation of Generic and Interchangeable

Medicines

RCSI Pharmacy Regulatory Affairs and Regulatory Authorities

RCSI Pharmacy Regulation of Medicine

St. Johns, Cork Veterinary Nursing Regulation of Veterinary Medicines

TCD Hospital Pharmacy Authorisation of Medicines

TCD Immunology Regulation of Medicines / Regulation of

Biological Medicines

TCD Pharmaceutical

Medicine Risk Management Plans: An Overview

TCD Pharmaceutical

Medicine Pharmacovigilance, Where are we Now?

TCD Pharmaceutical

Medicine

Communication of Drug Safety Data

TCD Pharmaceutical

Medicine The Role of CMDh


51

TCD Pharmaceutical

Medicine

Overview of the Pharmacovigilance Risk

Assessment Committee

TCD Pharmaceutical

Medicine Regulation of Biologicals

TCD Pharmaceutical

Medicine GCP Inspections

TCD Pharmaceutical

Medicine

Legal provisions Governing the SmPC, Package

Leaflet and Labelling

TCD Pharmaceutical

Medicine Traditional Herbal Medicinal Products (THMPs)

TCD Pharmaceutical

Medicine Quality Standards and Pharmacopoeias

TCD Pharmaceutical

Medicine Falsified Medicines Directive

TCD Pharmaceutical Sciences Regulation of Biologicals

TCD Pharmacy Overview of Pharmacovigilance

TCD Pharmacy Authorisation of Medicines and the Role of the

HPRA

TCD Pharmacy Quality Defect in Medicines

TCD Regulatory Affairs

Workshop Medical Devices Legislation

TCD Science The Role of the Regulatory Pharmacist

UCC

Laboratory Animal

Science and Training

(LAST)

Legislative and Regulatory Aspects of Scientific

Animal Protection

UCC PEARLL – Regulatory

Support of Innovation Innovation Benefits and Risks

UCC PEARLL – Regulatory

Support of Innovation

Process Analytical Technology and Continuous

Manufacturing

UCC Pharmacy Investigating and Reporting Quality Defects in

Medicines

UCC Pharmacy Regulation of Biological and Biosimilar

Medicines

UCD Bioengineering Medical Devices Legislation

UCD Clinical and Translational

Medicine Medical Devices Regulation and Innovation

UCD Nurse/Midwife

Prescribing The Role of the HPRA and Pharmacovigilance

UCD Regulatory Affairs and

Toxicology Medical Devices Legislation

UCD Regulatory Affairs and

Toxicology Pharmaceutical Regulatory Affairs


52

UCD Veterinary Medicine Regulation of Veterinary Medicines

University of

Copenhagen

Regulatory Affairs -

Biopharmaceuticals

Biosimilars: Quality, Non-clinical and Clinical

Requirements

REGULATORY PRESENTATIONS

Event/Organiser Presentation Title

AFI (European Clinical Trial Day) The Future of Clinical Research

Association of the European Self-

Medication Industry

Reclassification of Medicinal Products in the Irish

Regulatory Setting

BEAI Annual Conference Medical Device Innovation and Regulation

Beyond Compliance Meeting Medical Device Registries

BioProduction Congress Practical Advice on GMP Inspections

CASSS A Holistic Regulatory Approach to Accelerated CMC

Development

Cattle Association of Veterinary

Ireland Medicines Regulation - European Legislation Update

Chinese FDA New European Regulations on Medical Devices –

Perspective of the HPRA

Curam MedTech Minds Medical Device Regulation

DIA Benefit Risk Strategies

Workshop Referrals – Experience gained and Emerging Trends

DIA Conference Medical Device Regulation

DIA EuroMeeting 2017 SCOPE - Communicating Safety Information to Health

Care Professionals in Europe

EDQM How to Build a Good CEP Application - ICH Q3D

EMA Stakeholder Day Future Opportunities for Pharmacovigilance

EU Medical Device Clinical

Research Conference Medical Device Regulation

European Alliance for

Personalised Medicine Growth in Personalised Healthcare

GS1 Ireland Healthcare User

Group (HUG) Regulatory Update on Medical Devices

HISI Annual Conference Introduction to UDI in the MDR/IVDR

HISI Annual Conference Regulation of Medical Device Standalone Software

HSE (Registered Nurse

Prescribers) The HPRA’s Exempt Medicinal Products Programme


53

Irish Medtech Association Regulation of Medical Devices – Increasing Patient Safety

and Promoting Timely Innovation

Irish Medtech Association Sterility Assurance: Regulatory Expectations and

Common Deficiencies

Klifovet, Munich Veterinary Medicines: A Review and Look into the Future

of a National Competent Authority

MedTec Europe MEDDEV 2.7/1 Revision

MedTec Ireland Introduction to the new MDR

MedTec Ireland Medical Technology Sector in Ireland

National HPV Vaccine Conference Pharmacovigilance and HPV Vaccine

NUIG / HPRA Innovation

Workshop Regulatory Pathway for Medical Devices in Europe

NUIG / HPRA Innovation

Workshop HPRA Approach to CI Assessment under MDD

NSAI Notified Body Designation process

Official Medicines Control

Laboratory Network

Risk Assessment in Market Surveillance Testing

Programmes

Parenteral Drug Association,

Ireland

Exploring the Concept of Formality and Informality in

Quality Risk Management

PCR Innovators Day Medical Device Regulation

PDA Quality Risk Management

Workshop

Improvement Initiatives in relation to Quality Risk

Management

Pharmaceutical Inspection Co-

operation Scheme Validation Activities and Regulatory Expectations

Pharmig Annual Conference Contamination Control Strategy

PMDA, Japan Risk-based GMP Inspection Planning

QP Forum GMP Updates

Taking Care of Business

(Department of Business,

Enterprise and Innovation)

The Role of the HPRA and Our Support of Innovation

TÜV SÜD TAVI Valves

World Self-Medication Industry

Regulators Forum Innovation in Medicines Reclassification


54

Appendix 3 – Publications and Articles 2017

DRUG SAFETY NEWSLETTERS

Edition Articles

March

79th Edition

Fluconazole – reminder not to use in pregnancy

SGLT2 inhibitors and risk of lower limb amputation (mainly toe)

Reports of keratoacanthoma with ingenol mebutate

Adverse reaction reporting – reminder

Direct Healthcare Professional Communications published on the HPRA

website since the last Drug Safety Newsletter

April

80th Edition

Valproate-containing medicines – new EU review initiated

July

81st Edition

Valproate (Epilim) and Developmental Disorders: Update on ongoing EU

review

Domperidone-containing medicines: reminder of the risk of cardiac

adverse reactions-restricted indication, contraindications and reduced

dose and duration of use

New CPD e-learning module on reporting suspected adverse drug

reactions

August

82nd Edition

Daclizumab (Zinbryta) and risk of severe liver injury: initiation in multiple

sclerosis now restricted, promptly review patients already on treatment

Gabapentin – respiratory depression without concomitant opioid use

Amoxicillin; co-amoxiclav – very rare reports of DRESS (drug reaction

with eosinophilia and systemic symptoms)

November

83rd Edition

Quinine – reminder of safety profile and potential drug-drug

interactions particularly where used for nocturnal leg cramps

Flucloxacillin and concomitant paracetamol – risk of high anion

gap metabolic acidosis in very rare cases

Epoetins: new warnings on Severe Cutaneous Adverse Reactions

(SCARs)

Adverse reaction reporting during 2016

December

84th Edition

Conclusion of European Review of Gadolinium Contrast Agents –

Publication of European Commission Decision

December

85th Edition

Daclizumab (Zinbryta) and risk of severe liver injury – EU wide review

concludes and confirms further restrictions to reduce riskof liver

damage

New contraindication for injectable methylprednisoloneproducts

containing lactose (Solu-Medrone 40 mg / vial) in patients with cows’

milk allergy

Warning about the use of Xofigo (radium-223 dichloride) in

combination with Zytiga (abiraterone acetate) and prednisone or

prednisolone: ongoing clinical trial shows an increased risk of death and

fractures


55

HUMAN MEDICINES ARTICLES – EXTERNAL PUBLICATIONS

Month Publication Topic

January MIMS Otezla (apremilast) – Important advice regarding

suicidal ideation and behaviour

February IMF Miconazole and Warfarin – Reminder of the potential

for Interaction

MIMS Levetiracetam 100mg/ml Oral Solution- Global

reports of medication errors resulting in the

administration of higher than intended doses of

levetiracetam

March

MIMS Lenalidomide (Revlimid) – Advice regarding viral

reactivation

MIMS Respiratory

Supplement

Improved access to educational materials on the

HPRA website

MIMS Cardiovascular

Supplement

Miconazole and warfarin - Reminder of the potential

for interaction

April MIMS SGLT2 inhibitors and risk of lower limb amputation

(mainly toe)

May

MIMS Valproate-containing medicines – new EU review

initiated (main edition)

MIMS Oncology

Supplement

Reports of keratoacanthoma with ingenol mebutate

June

MIMS Fluconazole – reminder not to use in pregnancy

MIMS Respiratory

Supplement

Advice on potential interaction between cobicistat-

containing products and corticosteroids primarily

metabolised by CYP3A: risk of adrenal suppression

July/August

MIMS Domperidone-containing medicines: Reminder of

the risk of cardiac adverse reactions restricted

indication, contraindications and reduced dose and

duration of use

MIMS Diabetes

Supplement

SGLT2 inhibitors and risk of lower limb amputation

(mainly toe)

August IMF Domperidone-containing medicines: Reminder of the

risk of cardiac adverse reactions-restricted indication,

contraindications and reduced dose and duration of

use

September

MIMS Amoxicillin; co-amoxiclav – very rare reports of

DRESS (drug reaction with eosinophilia and systemic

symptoms)

MIMS Pain

Supplement

Gabapentin – respiratory depression without

concomitant opioid use

October MIMS Daclizumab (Zinbryta) and Risk of Severe Liver Injury:

Initiation in Multiple

Sclerosis Now Restricted, Promptly Review Patients

Already on Treatment

MIMS Women’s Health

Supplement

Reminder that Fluconazole Should Not be Used in

Pregnancy


56

November

MIMS Epoetins: New Warnings on Severe Cutaneous

Adverse Reactions (SCARs)

MIMS Diabetes

Supplement

High-Strength Insulin Preparations

December

MIMS New CPD e-learning module on reporting suspected

adverse drug reactions

MIMS Compendium Domperidone-containing medicines: Reminder of the

risk of cardiac adverse reactions restricted indication,

contraindications and reduced dose and duration of

use

HUMAN MEDICINES – PEER REVIEWED AND CONFERENCE PAPERS (HPRA CONTRIBUTORS)

Title Authors Publication / Event

Assessing awareness and attitudes

of healthcare professionals on the

use of biosimilar medicines: A

survey of physicians and

pharmacists in Ireland

O'Callaghan, J., Bermingham,

M., Leonard, M., Hallinan, F.,

Morris, J.M., Moore, U. and

Griffin, B.T.

Journal of Regulatory

Toxicology and

Pharmacology, 88, 252-

261

Knowledge of adverse drug

reaction reporting and the

pharmacovigilance of biological

medicines: A survey of healthcare

professionals in Ireland

O'Callaghan, J., Griffin B.T.,

Morris, J.M., and

Bermingham, M.

BioDrugs Journal

(accepted for

publication)





pharmacists in Ireland



Morris, J. M., Moore, U. and

Griffin, B. T.

Presentation, Irish

Nephrology Society

Annual Scientific

Meeting, Dublin, March

2017





pharmacists in Ireland’



Morris, J. M., Moore, U. and

Griffin, B. T.

Poster, All Ireland

Schools of Pharmacy

Conference, Cork, April

2017

VETERINARY MEDICINES ARTICLES – EXTERNAL PUBLICATIONS

Publication Topic

Veterinary Ireland Journal The regulation of the scientific and educational use of large

animals

Veterinary Ireland Journal Availability of veterinary medicinal products in Ireland

Veterinary Ireland Journal Antimicrobial resistance – update on European developments to

control it

It’s Your Field Care in use and disposal of sheep dips

It’s Your Field Exceptional authorisation of veterinary medicines

It’s Your Field Pharmacovigilance inspections


57

NEW INDUSTRY GUIDANCE DOCUMENTS

Document Title Month

Submission of Mock-Ups for Variations to Veterinary Products January

Placing Medical Device Standalone Software on the Market June

Scientific and Regulatory Advice for GXP activities October

Electronic Submissions – Medical Devices November

Notified Bodies – Designation Process November

Clinical Trials Regulation (EU) No. 536/2014 Pilot Project - Ireland December

Brexit Guidance - Human and Veterinary Medicines December

health products regulatory authority annual report 2017 · 9 applications for new clinical...

Documents